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FUNAKAMI Yoshinori


FacultyDepartment of Pharmacy
PositionAssociate Professor
Commentator Guide
Last Updated :2020/08/10

Education and Career

Academic & Professional Experience

  •   2011 , Lecturer, Faculty of Pharmacy, Kindai University

Research Activities

Research Interests

  • c-Fos

Published Papers

  • Emerging Evidence of Translational Control by AU-Rich Element-Binding Proteins., Otsuka H, Fukao A, Funakami Y, Duncan KE, Fujiwara T, Frontiers in genetics, Frontiers in genetics, 10, 332, 2019 , Refereed
  • Translation of Hepatitis A Virus IRES Is Upregulated by a Hepatic Cell-Specific Factor., Sadahiro A, Fukao A, Kosaka M, Funakami Y, Takizawa N, Takeuchi O, Duncan KE, Fujiwara T, Frontiers in genetics, Frontiers in genetics, 9, 307, 2018 , Refereed
  • Corneal Wound Healing Rate Delay in Ovariectomized Rats Receiving Low-calcium Diet., Nagai N, Ogata F, Funakami Y, Itoh Y, Kawasaki N, 30(11), 1623 - 1627, Nov. 2013 , Refereed
  • [A search for the risk factors for hiccups and evaluation of antiemetic therapy in CDDP-based chemotherapy, using cluster analysis]., Asano H, Watanabe M, Kawaguchi A, Yanae M, Funakami Y, Wada T, Matzno S, Yamazoe Y, Nishida S, Ichida S, Gan to kagaku ryoho. Cancer & chemotherapy, Gan to kagaku ryoho. Cancer & chemotherapy, 40(8), 1031 - 1036, Aug. 2013 , Refereed
  • Effects of the α1-adrenoceptor agonist phenylephrine on SART stress-induced orthostatic hypotension in rats., Funakami Y, Itoh E, Hata T, Wada T, Ichida S, BioPsychoSocial medicine, BioPsychoSocial medicine, 4, 13, Oct. 2010 , Refereed
  • An Experimental Animal Model for Orthostatic Hypotension : Repeatedly Cold-Stressed Rats with Autonomic Imbalance, Hata Taeko, Funakami Yoshinori, Itoh Eiji, Japanese Journal of Psychosomatic Medicine, Japanese Journal of Psychosomatic Medicine, 45(9), 697 - 706, Sep. 2005
    Summary:Rats stressed by specific alternation of rhythm in temperature (SART) show various symptoms of disautonomia, continuous hypotension and tachycardia. In our study, we investigated postural change-induced orthostatic hypotension (OH) in SART-stressed rats. Each rat was restrained on a board in a supine position under anesthesia. In the SART-stressed rats during rest, both systolic and diastolic blood pressure (BP) were low and heart rate was fast, as in awake rats. Postural change was caused by tilting the rat's head up at a 60°angle for 4min. As indexes of OH, three values were used : (1) the maximum decrease in BP, (2) the reflex ratio, and (3) the area enclosed by the baseline and the time-related BP curve (AUC). In comparison to unstressed rats, SART-stressed rats showed the following changes : the maximum decrease in BP was significantly larger, the reflex-induced recovery from the maximum decrease in BP was significantly smaller, and the AUC was significantly larger. Heart rate in the stressed rats decreased soon after tilting, while it increased in unstressed rats. We conclude that postural change in SART-stressed rats can be used as an animal model of OH.
  • Anxiety-like behavior in elevated plus-maze tests in repeatedly cold-stressed mice., Hata T, Nishikawa H, Itoh E, Funakami Y, Jpn J Pharmacol., Jpn J Pharmacol., 85(2), 189 - 196, Feb. 2001 , Refereed
  • Repeated Cold Stress Reduces Cyclophosphamide-Induced Cystitis/Bladder Pain and Macrophage Activity in Mice, Maho Tsubota, Tomoyoshi Miyamoto, Saki Hiruma, Haruka Saeki, Takaya Miyazaki, Fumiko Sekiguchi, Yoshinori Funakami, Atsufumi Kawabata, PHARMACOLOGY, PHARMACOLOGY, 99(5-6), 286 - 290, 2017 , Refereed
    Summary:We examined the effect of repeated cold (RC) stress on cyclophosphamide (CPA)-induced cystitis/bladder pain in mice, in relation to macrophage activity. CPA, given i.p. at 400 mg/kg, caused bladder pain symptoms accompanying cystitis in both unstressed and RC-stressed mice, which were prevented by the macrophage inhibitor minocycline. A low dose, that is, 200 mg/kg, of CPA still produced bladder pain symptoms in unstressed but not RC-stressed mice. Lipopoly-saccharide-induced cytokine production in peritoneal macrophages from RC-stressed mice was less than that from unstressed mice. Thus, RC stress appears to reduce CPA-induced bladder pain in mice, which may be associated with the decreased macrophage activity. (C) 2017 S. Karger AG, Basel
  • Repeated Cold Stress Enhances the Acute Restraint Stress-Induced Hyperthermia in Mice, Tomoyoshi Miyamoto, Yoshinori Funakami, Erika Kawashita, Ai Nomura, Nanako Sugimoto, Haruka Saeki, Maho Tsubota, Seiji Ichida, Atsufumi Kawabata, BIOLOGICAL & PHARMACEUTICAL BULLETIN, BIOLOGICAL & PHARMACEUTICAL BULLETIN, 40(1), 11 - 16, Jan. 2017 , Refereed
    Summary:The rodents exposed to repeated cold stress according to a specific schedule, known as specific alternation of rhythm in temperature (SART), exhibit autonomic imbalance, and is now used as an experimental model of fibromyalgia. To explore the susceptibility of SART-stressed animals to novel acute stress, we tested whether exposure of mice to SART stress for 1 week alters the extent of acute restraint stress-induced hyperthermia. Mice were subjected to 7-d SART stress sessions; i.e., the mice were alternately exposed to 24 and 4 degrees C at 1-h intervals during the daytime (09:00-16:00) and kept at 4 degrees C overnight (16:00-09:00). SART-stressed and unstressed mice were exposed to acute restraint stress for 20-60 min, during which rectal temperature was monitored. Serum corticosterone levels were measured before and after 60-min exposure to restraint stress. SART stress itself did not alter the body temperature or serum corticosterone levels in mice. Acute restraint stress increased the body temperature and serum corticosterone levels, both responses being greater in SART-stressed mice than unstressed mice. The enhanced hyperthermic responses to acute restraint stress in SART-stressed mice were significantly attenuated by SR59230A, a beta(3) adrenoceptor antagonist, but unaffected by diazepam, an anxiolytic, mifepristone, a glucocorticoid receptor antagonist, or indomethacin, a cyclooxygenase inhibitor. These results suggest that SART stress enhances the susceptibility of mice to acute restraint stress, characterized by increased hyperthermia and corticosterone secretion, and that the increased hyperthermic responses to acute stress might involve accelerated activation of sympathetic beta(3) adrenoceptors, known to regulate non-shivering thermogenesis in the brown adipose tissue.
  • Enhanced Hyperthermic Responses to Lipopolysaccharide in Mice Exposed to Repeated Cold Stress, Tomoyoshi Miyamoto, Yoshinori Funakami, Erika Kawashita, Shiori Tomita, Ai Nomura, Nanako Sugimoto, Haruka Saeki, Takaya Miyazaki, Maho Tsubota, Seiji Ichida, Atsufumi Kawabata, PHARMACOLOGY, PHARMACOLOGY, 99(3-4), 172 - 178, 2017 , Refereed
    Summary:Lipopolysaccharide (LPS) induces hyperthermia accompanied by various other systemic inflammatory symptoms. The rodents exposed to repeated cold (RC) stress according to a specific schedule are useful as experimental models for autonomic imbalance or fibromyalgia. It is now proven that RC-stressed mice exhibit tolerance to LPS, we examined thermal responses to LPS challenge in RC-stressed mice by monitoring core temperature using the telemetry system. Systemic administration of LPS caused bimodal hyperthermic responses in RC-stressed and unstressed mice. The magnitude of the LPS-induced hyperthermia was greater in RC-stressed mice than in unstressed mice. The RC stress-induced enhancement of hyperthermic responses to LPS was abolished by pretreatment with diclofenac, which is a cyclooxygenase (COX) inhibitor. LPS did not significantly increase COX-2 protein levels in the lung or hypothalamus of RC-stressed or unstressed mice. RC stress did not alter baseline serum corticosterone levels or their increases in response to LPS challenge. These results suggest that RC stress enhances the susceptibility of mice to LPS challenge, leading to greater prostanoid-dependent hyperthermia, which might contribute to tolerance to LPS in RC-stressed mice. (C) 2016 S. Karger AG, Basel.
  • Intravenous Administration of Cilostazol Nanoparticles Ameliorates Acute Ischemic Stroke in a Cerebral Ischemia/Reperfusion-Induced Injury Model, Noriaki Nagai, Chiaki Yoshioka, Yoshimasa Ito, Yoshinori Funakami, Hiroyuki Nishikawa, Atsufumi Kawabata, INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 16(12), 29329 - 29344, Dec. 2015 , Refereed
    Summary:It was reported that cilostazol (CLZ) suppressed disruption of the microvasculature in ischemic areas. In this study, we have designed novel injection formulations containing CLZ nanoparticles using 0.5% methylcellulose, 0.2% docusate sodium salt, and mill methods (CLZ(nano) dispersion; particle size 81 +/- 59 nm, mean +/- S.D.), and investigated their toxicity and usefulness in a cerebral ischemia/reperfusion-induced injury model (MCAO/reperfusion mice). The pharmacokinetics of injections of CLZ(nano) dispersions is similar to that of CLZ solutions prepared with 2-hydroxypropyl--cyclodextrin, and no changes in the rate of hemolysis of rabbit red blood cells, a model of cell injury, were observed with CLZ(nano) dispersions. In addition, the intravenous injection of 0.6 mg/kg CLZ(nano) dispersions does not affect the blood pressure and blood flow, and the 0.6 mg/kg CLZ(nano) dispersions ameliorate neurological deficits and ischemic stroke in MCAO/reperfusion mice. It is possible that the CLZ(nano) dispersions will provide effective therapy for ischemic stroke patients, and that injection preparations of lipophilic drugs containing drug nanoparticles expand their therapeutic usage.
  • Phloridzin-sensitive transport of echinacoside and acteoside and altered intestinal absorption route after application of Cistanche tubulosa extract, Tadatoshi Tanino, Noriaki Nagai, Yoshinori Funakami, JOURNAL OF PHARMACY AND PHARMACOLOGY, JOURNAL OF PHARMACY AND PHARMACOLOGY, 67(10), 1457 - 1465, Oct. 2015 , Refereed
    Summary:ObjectivesThe objective of this study was to address the beneficial effects of Cistanche tubulosa extract on improving the low intestinal permeability of echinacoside (ECH) and acteoside (ACT).MethodsAbsorption of ECH and ACT in C.tubulosa extract was characterized using human intestinal Caco-2 cell monolayers with intact compounds. Glucose transporter-dependent absorption of ECH and ACT was confirmed by an in-situ intestinal perfusion technique.Key findingsThe apparent permeability (P-app) was not significantly different between intact ECH and intact ACT. In the presence of phloridzin, the P-app of the ECH and ACT at a high dose was reduced to 20% of the respective non-treatment, but was not altered by phloretin and verapamil. C.tubulosa extract at low and high doses enhanced the P-app of ECH and ACT (both by threefold), resulting in their large participation in sodium-dependent glucose transporter-independent absorption. At a low concentration, concomitant ECH and ACT levels in portal blood were significantly suppressed by phloridzin.ConclusionThe dietary and medicinal C.tubulosa extract enhancing the intestinal absorption of ECH and ACT may serve to better manage human health, although the involvement of phloridzin-sensitive transport should be reduced.
  • Cyclosporin A-sensitive cytotoxicity of flurbiprofen non-stereoselectively mediated by cytochrome P450 metabolism in three-dimensional cultured rat hepatocytes, Tadatoshi Tanino, Yoshinori Funakami, Noriaki Nagai, Yoshihisa Kato, JOURNAL OF PHARMACY AND PHARMACOLOGY, JOURNAL OF PHARMACY AND PHARMACOLOGY, 67(10), 1406 - 1415, Oct. 2015 , Refereed
    Summary:Objectives2-Arylpropionic acid (profen) drugs are associated with severe hepatotoxicity; however, risk factors are still poorly understood. Acyl-coenzyme A (acyl-CoA) thioesters of profen drugs play a more important role in the covalent binding to rat hepatocyte proteins than the respective acyl-glucuronides. Therefore, we examined whether acyl-glucuronides, acyl-CoA thioesters and oxidative metabolites of profen drugs stereoselectively participated in liver damage.MethodsCytotoxicity was determined by measuring lactate dehydrogenase (LDH) leakage from three-dimensional cultured rat hepatocytes.Key findingsLDH leakage was not induced by R-2-phenylpropionic acid and R-ibuprofen greatly forming acyl-CoA thioesters. S-Naproxen metabolized mainly by Uridine 5-diphosphate (UDP)-glucuronosyl-transferase did not enhance LDH leakage. However, flurbiprofen (FLP) induced LDH leakage. A selective cytochrome P450 (CYP) 2C11 inhibitor suppressed 40-50% of the R-FLP and S-FLP-induced cytotoxicity. Borneol non-stereoselectively accelerated the FLP-induced cytotoxicity. The R-FLP-induced cytotoxicity decreased intracellular adenosine triphosphate (ATP) levels to 50% of untreated hepatocytes. An inhibitor of mitochondrial permeability transition pore, cyclosporin A (Cys A), rescued ATP levels and LDH leakage back to control levels.ConclusionThe reactive acyl-CoA thioesters and acyl-glucuronides were not associated with liver damage, denying one of the leading hypotheses. CYP metabolism of FLP non-stereoselectively participated in Cys A-sensitive cytotoxicity, suggesting mitochondrial injury.
  • Hypercalcemia Leads to Delayed Corneal Wound Healing in Ovariectomized Rats, Noriaki Nagai, Fumihiko Ogata, Naohito Kawasaki, Yoshimasa Ito, Yoshinori Funakami, Norio Okamoto, Yoshikazu Shimomura, BIOLOGICAL & PHARMACEUTICAL BULLETIN, BIOLOGICAL & PHARMACEUTICAL BULLETIN, 38(7), 1063 - 1069, Jul. 2015 , Refereed
    Summary:Hypercalcemia is often observed in postmenopausal women as well as in patients with primary hyperparathyroidism or malignant tumors. In this study, we investigated the relationship between calcium ion (Ca2+) levels in lacrimal fluid and the rate of corneal wound healing in hypercalcemia using ovariectomized (OVX) rat debrided corneal epithelium. We also determined the effects of Ca2+ levels on cell adhesion, proliferation and viability in a human cornea epithelial cell line (HCE-T). The calcium content in bones of OVX rats decreased after ovariectomy. Moreover, the Ca2+ content in the blood of OVX rats was increased 1 month after ovariectomy, and decreased. The Ca2+ content in the lacrimal fluid of OVX rats was also increased after ovariectomy, and then decreased similarly as in blood. Corneal wound healing in OVX rats was delayed in comparison with Sham rats (control rats), and a close relationship was observed between the Ca2+ levels in lacrimal fluid and the rate of corneal wound healing in Sham and OVX rats (y=-0.7863x+8.785, R=0.78, n=25). In addition, an enhancement in Ca2+ levels caused a decrease in the viability in HCE-T cells. It is possible that enhanced Ca2+ levels in lacrimal fluid may cause a decrease in the viability of corneal epithelial cells, resulting in a delay in corneal wound healing. These findings provide significant information that can be used to design further studies aimed at reducing corneal damage of patients with hypercalcemia.
  • PKC/MEK inhibitors suppress oxaliplatin- induced neuropathy and potentiate the antitumor effects, Masanobu Tsubaki, Tomoya Takeda, Tadahumi Tani, Hirotaka Shimaoka, Naohiro Suzuyama, Kotaro Sakamoto, Arisa Fujita, Naoki Ogawa, Tatsuki Itoh, Motohiro Imano, Yoshinori Funakami, Seiji Ichida, Takao Satou, Shozo Nishida, INTERNATIONAL JOURNAL OF CANCER, INTERNATIONAL JOURNAL OF CANCER, 137(1), 243 - 250, Jul. 2015 , Refereed
    Summary:Oxaliplatin is a key drug commonly used in colorectal cancer treatment. Despite high clinical efficacy, its therapeutic application is limited by common, dose-limiting occurrence of neuropathy. As usual symptomatic neuropathy treatments fail to improve the patients' condition, there is an urgent need to advance our understanding of the pathogenesis of neuropathy to propose effective therapy and ensure adequate pain management. Oxaliplatin-induced neuropathy was recently reported to be associated with protein kinase C (PKC) activation. It is unclear, however, whether PKC inhibition can prevent neuropathy. In our current studies, we found that a PKC inhibitor, tamoxifen, inhibited oxaliplatin-induced neuropathy via the PKC/extracellular signal-regulated kinase (ERK)/c-Fos pathway in lumbar spinal cords (lumbar segments 4-6). Additionally, tamoxifen was shown to act in synergy with oxaliplatin to inhibit growth in tumor cells-implanted mice. Moreover, mitogen-activated protein kinase kinase (MEK) 1/2 inhibitor, PD0325901, suppressed oxaliplatin-induced neuropathy and enhanced oxaliplatin efficacy. Our results indicate that oxaliplatin-induced neuropathy is associated with PKC/ERK/c-Fos pathway in lumbar spinal cord. Additionally, we demonstrate that disruption of this pathway by PKC and MEK inhibitors suppresses oxaliplatin-induced neuropathy, thereby suggesting that PKC and MEK inhibitors may be therapeutically useful in preventing oxaliplatin-induced neuropathy and could aid in combination antitumor pharmacotherapy.
  • Differential Expression of the 5-HT3A and 5-HT3B Receptor in Differentiated NG108-15 Cells, Hajime Asano, Akinori Miyamoto, Mariko Nakao, Chiyuki Wakaki, Takuma Iida, Yoshinori Funakami, Tetsuyuki Wada, Seiji Ichida, NEUROCHEMICAL RESEARCH, NEUROCHEMICAL RESEARCH, 37(8), 1738 - 1746, Aug. 2012 , Refereed
    Summary:Previous work from this laboratory has shown that the serotonin (5-HT) induced response is significantly augmented in differentiated NG108-15 (NG) cells treated with dibutyryl cAMP (Bt(2)cAMP) due to qualitative and quantitative changes in the expression of the 5-HT3 receptor as demonstrated by specific [H-3] LY-278584 (a selective 5HT(3) receptor antagonist) binding. In this study, we investigated whether there is any change in the relative expression of the 5-HT3A and 5-HT3B subunits in NG cells differentiated following Bt(2)cAMP treatment cells. The major findings of this study were that the relative amount of 5-HT3B subunit mRNA in Bt(2)cAMP-treated NG cells 5 days following Bt(2)cAMP-treatment was greater than that in the untreated cells. In contrast, the relative expression of the 5-HT3B subunit protein in the Bt(2)cAMP-treated NG cells was much less than in the untreated cells, but the relative expression of the 5-HT3A subunit in the Bt(2)cAMP-treated NG cells was similar to the untreated cells. Therefore, no relationship between mRNA and protein expression for 5-HT3A and 5-HT3B subunits in Bt(2)cAMP treated and untreated NG cells were observed. It was also found that fluorescent intensity for the 5-HT3B subunit in the cell body of the Bt(2)cAMP treated and untreated NG cells gradually decreased from the day 1-5 after Bt(2)cAMP treatment. However, in specific areas such as the varicosity and nerve endings of the Bt(2)cAMP treated cells, staining intensity for the 5-HT3B subunits was stronger than in the untreated cells at the all time points, peaking at day 5 post-treatment. These results suggest that the augmented response induced by 5-HT acting via 5-HT3 receptors in differentiated NG cells may be due to changes in the relative amount of the 5-HT3B subunit, particularly the ratio and distribution of the 5-HT3A to (3B) subunits.
  • Specific Alternation of Rhythm in Temperature (SART) Stress-Induced Irritable Bowel Syndrome-Like Changes in Mice and Effects of Drugs, Yoshinori Funakami, Eiji Itoh, Taeko Hata, Tetsuyuki Wada, Seiji Ichida, BIOLOGICAL & PHARMACEUTICAL BULLETIN, BIOLOGICAL & PHARMACEUTICAL BULLETIN, 33(9), 1545 - 1549, Sep. 2010 , Refereed
    Summary:Stress is closely associated with the manifestation and progress of irritable bowel syndrome (IBS). For the purpose of establishing experimentally the relationship between IBS and stress, the transportation capacity of the small intestine in specific alternation of rhythm in temperature (SART)-stressed animals was studied using charcoal transportation method. The charcoal suspension was administered orally into the stomach of fasting mice. Mice were sacrificed after a certain time and %charcoal transit (%CT) of the small intestine was measured. The %CTs in SART-stressed mice were greater than those in unstressed or continuously cold-stressed mice. This increase in %CT remained for I week after discontinuation of SART stress loading. Cholinergic blockers decreased %CTs in SART-stressed mice. Increases in %CT by a cholinesterase inhibitor were less in SART-stressed mice than in unstressed mice. Increases of %CT in SART-stressed mice were suppressed by Neurotropine. These results suggested that the parasympathetic hypertonicity, not just cold, played a role in the increases in the transportation capacity in SART-stressed mice and that these animals can be a useful tool for elucidation of the mechanism of IBS.
  • Changes in Characteristics of the Specific Binding of [H-3]LY-278584, a 5-HT3-Receptor Antagonist, on Differentiated NG108-15 Cells, Kayoko Matsushima, Takashi Imanishi, Hajime Asano, Yoshinori Funakami, Tetsuyuki Wada, Seiji Ichida, JOURNAL OF PHARMACOLOGICAL SCIENCES, JOURNAL OF PHARMACOLOGICAL SCIENCES, 113(3), 281 - 284, Jul. 2010 , Refereed
    Summary:We have reported previously that the concentration of intracellular Ca2+ evoked by serotonin (5-HT) was significantly augmented in differentiated NG108-15 (NG) cells treated with dibutyryl cAMP and the enhanced response occurred via 5-HT3 receptors. We investigated changes in the characteristics for specific binding of [H-3]LY-278584 (a specific antagonist of the 5-HT3 receptor) on membranes from differentiated NG cells. The results indicated that the K-d and B-max values for the specific binding to differentiated NG cells were significantly smaller and larger, respectively, than those for undifferentiated NG cells. The binding was significantly inhibited by 10 nM tropisetron, a specific 5-HT3 receptor antagonist, but not by any other types of 5-HT receptor antagonists. These results suggested that the enhanced response by 5-HT in differentiated NG cells was due to both qualitative and quantitative changes in the 5-HT3 receptor.
  • Characteristics for Enhanced Response of Serotonin-Evoked Ion Dynamics in Differentiated NG108-15 Cells, Takashi Imanishi, Kayoko Matsushima, Akinori Kawaguchi, Hajime Asano, Yoshinori Funakami, Tetsuyuki Wada, Takashi Masuko, Shigeru Yoshida, Seiji Ichida, NEUROCHEMICAL RESEARCH, NEUROCHEMICAL RESEARCH, 34(5), 1011 - 1019, May 2009 , Refereed
    Summary:Characteristics for the up-regulated response in the concentration of intracellular calcium ion ([Ca(2+)] (i) ) and in the sodium ion (Na(+)) current by serotonin (5-HT) were investigated in differentiated neuroblastoma x glioma hybrid NG108-15 (NG) cells. The results for the changes in [Ca(2+)] (i) by 5-HT were as follows, (1) The 5-HT-induced Ca(2+) response was inhibited by 3 x 10(-9) M tropisetron (a 5-HT(3) receptor blocker), but not by other types of 5-HT receptor blockers; (2) The 5-HT-induced Ca(2+) response was mainly inhibited by calciseptine (a L-type Ca(2+) blocker), but not by other types of Ca(2+) channel blockers or 10(-7) M TTX (a voltage-sensitive Na(+) channel blocker); (3) When the extracellular Na(+) was removed by exchange with choline chloride or N-methyl-d-glucamine, the 5-HT-induced Ca(2+) response was extremely inhibited. The results for the 5-HT-induced Na(+) current by the whole cell patch-clamp technique were as follows, (1) The 5-HT-induced Na(+) current in differentiated cells was significantly larger than that in undifferentiated cells; (2) The ED(50) value for 5-HT-induced Na(+) current in undifferentiated and differentiated cells was almost the same, about 4 x 10(-6) M each other; (3) The 5-HT-induced Na(+) current was completely blocked by 3 x 10(-9) M tropisetron, but not by other 5-HT receptor antagonists and 10(-7) M TTX. These results suggested that 5-HT-induced Ca(2+) response in differentiated NG cells was mainly due to L-type voltage-gated Ca(2+) channels allowing extracellular Na(+) to enter via 5-HT(3) receptors, but not through voltage-gated Na(+) channels.
  • Effects of some beta-adrenoceptor antagonists on orthostatic hypotension in repeatedly cold-(SART-) stressed rats, Yoshinori Funakami, Taeko Hata, Eiji Itoh, Seigo Itano, BIOLOGICAL & PHARMACEUTICAL BULLETIN, BIOLOGICAL & PHARMACEUTICAL BULLETIN, 30(2), 303 - 308, Feb. 2007 , Refereed
    Summary:Rats stressed by specific alternation of rhythm in temperature (SART) show various symptoms of disautonomia, increased pulse rates, continuous hypotension, and severe orthostatic hypotension (OH) when they are subjected to postural change. The OH symptoms are improved by muscarinic M-2-receptor blockers. In the present study, effects of beta-adrenoceptor blocking agents on OH in SART-stressed rats were investigated. Anesthetized rats were restrained on a board in the supine position, and direct blood pressure and ECG were measured automatically using Fluclet (R) Jr.2. Postural change was performed by raising the rat's head up to a 60 degrees angle for 4 min. Unstressed rats treated with hexamethonium showed large decrease in blood pressure, small reflex from the bottom of pressure and decreased tachycardia reflex, whereas isoproterenol showed little changes. In SART-stressed rats, isoproterenol alleviated the decrease in blood pressure in postural change, brought large reflex from the bottom of pressure and increased tachycardia reflex, whereas hexamethonium had little changes. Propranolol and atenolol induced the similar changes as those seen by hexamethonium. ICI-118,551, a selective beta(2)-adrenoceptor antagonist showed large reflex from the bottom of pressure and increased tachycardia reflex in stressed rats, whereas little changes in unstressed rats. In conclusion, it was suggested that the hypotension in OH manifestation time of rats reflects the state of peripheral blood vessels, and beta(1)-adrenoceptors played a role in compensatory tachycardia reflex and beta(2)-adrenoceptors in blood pressure reflex. The circulatory regulation in SART-stressed rats seems to be poorly functioning in nervous reflex in postural changes.
  • Effects of AF-DX116 and other muscarinic receptor antagonists on orthostatic hypotension in autonomic imbalanced (SART-Stressed) rats, T Hata, Y Funakami, E Itoh, JOURNAL OF PHARMACOLOGICAL SCIENCES, JOURNAL OF PHARMACOLOGICAL SCIENCES, 97(3), 386 - 392, Mar. 2005 , Refereed
    Summary:SART (specific alternation of rhythm in temperature)-stressed rats are an animal model of autonomic imbalance created by exposing animals to repeated cold stress. The SART-stressed rats have been shown to easily develop orthostatic hypotension (OH). In this study, effects of AF-DX116, a selective M-2 antagonist, and other muscarinic receptor antagonists on OH were investigated in SART-stressed and unstressed rats. Each anesthetized rat was canulated into the left common carotid artery, and blood pressure (BP) and heart rate were measured. Stimulation for postural change was initiated by head-up tilting. As the indices of OH, the maximum fall of BP, % reflex (recovery from maximum fall), and the area enclosed between the baseline and the recovery Curve for BP (AUC) were used. Large AUC and small % reflex in SART-stressed rats were changed, becoming similar to those of the unstressed rats by AF-DX116 and methoctoramine. Atropine and methylatropine had similar effects to AF-DX116. However, the effects of methoctoramine, atropine, and methylatropine were less than that of AF-DX116. Pirenzepine was not effective. In conclusion, it was suggested in SART-stressed rats that OH was related to hyperactivity in the parasympathetic nerve and the M2 receptor played the major role in OH.
  • A role for corticotropin-releasing factor in repeated cold stress-induced anxiety-like behavior during forced swimming and elevated plus-maze tests in mice, H Nishikawa, T Hata, E Itoh, Y Funakami, BIOLOGICAL & PHARMACEUTICAL BULLETIN, BIOLOGICAL & PHARMACEUTICAL BULLETIN, 27(3), 352 - 356, Mar. 2004 , Refereed
    Summary:SART (specific alternation of rhythm in temperature) stress is known to cause anxiety-like behavior in mice/rats in several anxiety-related behavioral tests. In the present study, we investigated possible roles for corticotropin-releasing factor (CRF) and glucocorticoids in SART stress-induced anxiety-like behavior in two different anxiety-related behavioral tests. In the forced swimming test, CRF, administered intracerebroventricular (i.c.v.) at 0.5-2 pmol/mouse, dose-dependently reduced immobility time in unstressed and SART-stressed mice. alpha-Helical CRF, a specific CRIT receptor antagonist, administered i.c.v. at 0.1-1 nmol/mouse, dose-dependently increased immobility time in SART-stressed mice, but not in unstressed mice. In the elevated plus-maze test, CRF at 10-20 pmol/mouse significantly decreased the time spent in open arms in unstressed mice. CRF at a high dose tended to decrease this time in SART-stressed mice, but this decrease was not statistically significant. alpha-Helical CRIT failed to modify the time in unstressed mice. In contrast, alpha-helical CRF at 0.38 and 0.75 nmol/mouse increased the time in SART-stressed mice. Both immobility time in the forced swimming test and time spent in open arms in the elevated plus-maze test in unstressed and SART-stressed mice were unaffected by adrenalectomy. These results suggest that CRIT plays an important role in anxiety-like behavior caused by SART stress.
  • Blood pressure and heart rate are increased by AF-DX 116, a selective M-2 antagonist, in autonomic imbalanced and hypotensive rats caused by repeated cold stress, T Hata, E Itoh, Y Funakami, K Ishida, S Uchida, JAPANESE JOURNAL OF PHARMACOLOGY, JAPANESE JOURNAL OF PHARMACOLOGY, 85(3), 313 - 321, Mar. 2001 , Refereed
    Summary:Rats exposed to SART (specific alternation of rhythm in temperature) stress, which are ideal animal models for vagotonia-type dysautonomia, show various changes in cardiac and circulatory systems. In this study, attention was directed to cholinergic function in the SART-stressed rat heart and the effects of AF-DX 116, a specific muscarinic M-2 antagonist, on blood pressure and heart rate. The results were compared with those obtained for atropine and pirenzepine. In SART-stressed rats, systolic and diastolic blood pressures (SBP and DBP) were lower than in unstressed rats. Oral AF-DX 116 resulted in greater elevation of DBP than SEP in unstressed rats. In stressed rats, greater and more prolonged elevation of SEP than in unstressed rats was noted, particularly at higher doses. A dose-dependent SEP change in stressed rats, caused by intravenous AF-DX 116, was shifted upward in parallel with that in unstressed groups, unlike with oral administration The positive chronotropic effect of this drug was smaller in stressed rats than in unstressed rats, in contrast to the presser effect. SART-stressed rats may thus have an enhanced sympathetic tone in the heart, as well as changes in muscarinic M-2 receptors at sympathetic nerve endings and at the heart muscle. The effects of AF-DX 116 on blood pressure and heart rate thus may arise from peripheral action and AF-DX 116 may be useful for treating hypotension related to autonomic imbalance of the vagotonia type.


  • in vitro翻訳システムを用いたmiRNAによる翻訳制御分子機構の解析, 深尾亜喜良, 友廣拓生, 大塚衆志, 青山智彦, 船上仁範, 足達俊吾, 夏目徹, 藤原俊伸, 日本RNA学会年会要旨集, 19th, 153,   2017 07 19 ,
  • ARE結合タンパク質AUF1による遺伝子発現制御機構の解析, 西阪皓理, 松木香菜子, 大塚衆志, 深尾亜喜良, 船上仁範, 藤原俊伸, 日本RNA学会年会要旨集, 19th, 154,   2017 07 19 ,
  • BRF1によるmRNA分解と共役した翻訳抑制機構の解析, 大塚衆志, 武知美和, 深尾亜喜良, 船上仁範, 藤原俊伸, 日本RNA学会年会要旨集, 19th, 158,   2017 07 19 ,
  • 哺乳類におけるmiRISCによる翻訳抑制機構の解明, 坂村由梨佳, 友廣拓生, 大塚衆志, 深尾亜喜良, 船上仁範, 鈴木亨, 山本雅, 藤原俊伸, 日本RNA学会年会要旨集, 19th, 80,   2017 07 19 ,
  • Effect of Extract Containing Metabolic Products of Bacillus Subtilis Natto on Hypertension in SHR and SHR-SP Rats, 長井紀章, 真野裕, 船上仁範, 緒方文彦, 伊藤吉將, 後藤和子, 川崎直人, 医療薬学, 43, 2, 72‐79, 79,   2017 02 10 , 10.5649/jjphcs.43.72,
    Summary:<p>We investigated the preventive effect of extract containing metabolic products of <i>Bacillus subtilis natto</i> (NFE extract) on essential hypertension. The spontaneously hypertensive rat (SHR rat) and stroke-prone SHR rat (SHR-SP rat) were used in this study, and the NFE extract was administered by free drinking for 6-14 weeks of age (6, 7 weeks of age, 25 mL/day/rat; 8-14 weeks of age, 30 mL/day/rat). The administration of NFE extract did not affect the food intake and body weight in the WKY, SHR and SHR-SP rats. Significant changes in systolic (SBP) and diastolic (DBP) blood pressure levels between WKY rats administered with and without NFE extract were not observed for rats 6-14 weeks of age. On the other hand, the SBP and DBP in SHR and SHR-SP rats increased with aging, and the administration of NFE extract significantly attenuated the increased SBP, DBP in SHR and SHR-SP rats. In conclusion, the administration of NFE extract prevents increased blood pressure in SHR and SHR-SP rats. These findings provide significant information that can be used to design further studies aimed at elucidating the precise mechanism for decrease of blood pressure by NFE extract.</p>
  • BRF1によるmRNA分解と共役した翻訳抑制機構の解析, 武知美和, 大塚衆志, 深尾亜喜良, 船上仁範, 藤原俊伸, 日本生化学会大会(Web), 90th, ROMBUNNO.2LBA‐067 (WEB ONLY),   2017 ,
  • 納豆による高血圧予防効果の解明:納豆菌酵素発酵代謝物は本態性高血圧の発症を抑制する, 長井紀章, 真野裕, 船上仁範, 緒方文彦, 伊藤吉將, 後藤和子, 川崎直人, 日本薬学会年会要旨集(CD-ROM), 137th, ROMBUNNO.26PB‐am120,   2017 ,
  • Survey on Customer Satisfaction for Evaluation and Improvement of Physical Assessment Practical Training Seminar for Pharmacists, 大鳥徹, 井上知美, 細見光一, 中川博之, 高島敬子, 近藤尚美, 高田亜美, 伊藤栄次, 中山隆志, 和田哲幸, 石渡俊二, 前川智弘, 船上仁範, 中村真也, 窪田愛恵, 平出敦, 松山賢治, 西田升三, 社会薬学, 35, 2, 101, 101,   2016 12 10 , 10.14925/jjsp.35.2_94,
    Summary:フィジカルアセスメント講習会に参加した143名を対象にアンケートを実施した。CS分析(Customer Satisfaction analysis)とテキストマイニングにより検討した。男性が39%、女性が61%と女性が多かった。勤務先は保険調剤薬局が38%、病院が62%となっており、病院勤務者が多かった。改善度は、数値が大きいほど改善の優先順位は高くなるが、改善度の値が大きい順に五つ項目を上げると、「心電図の読み方」「呼吸音の聴診」「SBAR」「時間は適当でしたか」「心音の聴診」であった。CSグラフにおいて、優先的に改善する必要がある項目がプロットされる「要改善項目」(第4象限)として抽出されてきたのは、「呼吸音の聴診」、「SBAR」であった。「心音・腸音の聴診」、「心電図の読み方」、「血圧測定」は評価が低く、総合評価への影響度も低い項目である「改善検討項目」として第3象限にプロットされた。「講義内容」、「症例に興味が持てたか」、「フィジカルアセスメントモデルの機能」、「時間は適当でしたか」は評点が高く、総合評価への影響度も高い項目である「重要維持項目」として第1象限にプロットされた。
  • 乾式遊星ボールミル・湿式ビーズミル法の組み合わせによるナノ医薬品の創製:シロスタゾールナノ結晶からなる注射用製剤は脳虚血を抑制する, 上野祥奈, 長井紀章, 松田茅裕, 岩前亜弥, 伊藤吉將, 船上仁範, 西川裕之, 川畑篤史, 日本油化学会年会講演要旨集, 55th, 294,   2016 09 07 ,
  • PABP interacting protein1(Paip1)による翻訳制御機構の解析, 青山智彦, 大塚衆志, 船上仁範, 深尾亜喜良, 藤原俊伸, 日本分子生物学会年会プログラム・要旨集(Web), 39th, ROMBUNNO.3LBA‐023 (WEB ONLY),   2016 ,
  • cap依存的翻訳におけるeIF4Hの機能解析, 友廣拓生, 深尾亜喜良, 船上仁範, 藤原俊伸, 日本分子生物学会年会プログラム・要旨集(Web), 39th, ROMBUNNO.3LBA‐024 (WEB ONLY),   2016 ,
  • RNA結合タンパク質HuDによる翻訳促進機構の素過程の解析, 大塚衆志, 深尾亜喜良, 船上仁範, 藤原俊伸, 日本分子生物学会年会プログラム・要旨集(Web), 39th, ROMBUNNO.3LBA‐026 (WEB ONLY),   2016 ,
  • RNA結合タンパク質が仲介するmRNA分解と翻訳との共役, 武知美和, 深尾亜喜良, 船上仁範, 藤原俊伸, 日本分子生物学会年会プログラム・要旨集(Web), 39th, ROMBUNNO.3LBA‐027 (WEB ONLY),   2016 ,
  • ポリオウイルスの細胞種特異的なIRES依存的翻訳の解析, 貞廣暁利, 足達俊吾, 深尾亜喜良, 船上仁範, 夏目徹, 竹内理, 藤原俊伸, 日本分子生物学会年会プログラム・要旨集(Web), 39th, ROMBUNNO.3LBA‐022 (WEB ONLY),   2016 ,
  • CS分析(Customer Satisfaction analysis)による薬剤師のためのフィジカルアセスメント講習会の評価と改善項目の抽出, 大鳥徹, 井上知美, 細見光一, 伊藤栄次, 中山隆志, 和田哲幸, 石渡俊二, 船上仁範, 中村真也, 平出敦, 窪田愛恵, 松山賢治, 西田升三, 日本医療薬学会年会講演要旨集, 25th, 491,   2015 10 23 ,
  • SARTストレス誘発肺胞マクロファージ貪食能低下に対するβ2受容体刺激薬サルブタモールの改善効果とそのシグナル伝達経路について, 植芝慧子, 大友栞, 杉原小雪, 山村愛美, 船上仁範, 和田哲幸, 市田成志, 日本薬学会年会要旨集(CD-ROM), 135th, ROMBUNNO.28PB-AM139S,   2015 ,
  • SARTストレスによる肺胞マクロファージの貪食能低下は交感神経系の活性化によって改善する, 植芝慧子, 船上仁範, 田代のぞみ, 西島知里, 大友栞, 杉原小雪, 阪井邦正, 和田哲幸, 市田成志, 日本薬学会年会要旨集(CD-ROM), 134th, ROMBUNNO.28PMM-155S,   2014 ,
  • 細胞内カリウム濃度上昇は神経細胞分化を誘導する, 春木恵, 和田哲幸, 藤木亮, 植芝慧子, 船上仁範, 武智昌幸, 吉田繁, 市田成志, 生体機能と創薬シンポジウム要旨集, 2014, 97,   2014 ,
  • 細胞ストレスとカリウムイオンチャネルの関係について, 和田哲幸, 古賀雅也, 阪井邦正, 植芝慧子, 船上仁範, 吉田繁, 武智昌幸, 市田成志, 日本薬学会年会要旨集(CD-ROM), 134th, ROMBUNNO.28AMM-125,   2014 ,
  • SARTストレス誘発肺胞マクロファージの機能異常に対する自律神経系の関与, 植芝慧子, 大友栞, 杉原小雪, 山村愛美, 船上仁範, 和田哲幸, 市田成志, 生体機能と創薬シンポジウム要旨集, 2014, 95,   2014 ,
  • Corneal Wound Healing Rate Delay in Ovariectomized Rats Receiving Low-calcium Diet, 長井紀章, 緒方文彦, 船上仁範, 伊藤吉將, 川崎直人, あたらしい眼科, 30, 11, 1623, 1627,   2013 11 30 ,
  • A Search for the Risk Factors for Hiccups and Evaluation of Antiemetic Therapy in CDDP-Based Chemotherapy, Using Cluster Analysis, 浅野肇, 渡辺瑞貴, 川口明範, 柳江正嗣, 船上仁範, 和田哲幸, 松野純男, 山添譲, 西田升三, 市田成志, 癌と化学療法, 40, 8, 1031, 1036,   2013 08 15 ,
  • チメロサールのイオンチャネルに対する影響について, 和田哲幸, 吉田泰介, 久保田大樹, 山田愛, 浅野肇, 阪井邦正, 植芝慧子, 船上仁範, 南武, 吉田繁, 市田成志, 日本薬学会年会要旨集(CD-ROM), 133rd, ROMBUNNO.28PMC-102,   2013 ,
  • SARTストレスマウスにおける血清アンチエイジング及びストレスホルモンの変化―コルチコステロンとデヒドロエピアンドロステロン―, 阪井邦正, 船上仁範, 岸本茉希, 谷口友梨, 豊田和, 大浦沙貴子, 岡部由季, 植芝慧子, 浅野肇, 和田哲幸, 市田成志, 日本薬学会年会要旨集(CD-ROM), 133rd, ROMBUNNO.29AMC-203S,   2013 ,
  • SARTストレスにより低下した肺胞マクロファージの貪食能はアドレナリンβ2受容体を介して改善する, 植芝慧子, 船上仁範, 田代のぞみ, 西島知里, 大友栞, 杉原小雪, 浅野肇, 阪井邦正, 和田哲幸, 市田成志, 日本薬学会年会要旨集(CD-ROM), 133rd, ROMBUNNO.28AMD-030S,   2013 ,
  • ウワバインの細胞保護作用とカリウムイオンチャネルの関係について, 古賀雅也, 和田哲幸, 藤木亮, 阪井邦正, 植芝慧子, 浅野肇, 船上仁範, 武智昌幸, 市田成志, 日本薬学会年会要旨集(CD-ROM), 133rd, ROMBUNNO.28PMC-103,   2013 ,
  • 神経細胞の分化と細胞内カリウム濃度の関係, 和田哲幸, 藤木亮, 淺野肇, 船上仁範, 武智昌幸, 吉田繁, 市田成志, 日本生化学会大会(Web), 86th, 3P-270 (WEB ONLY),   2013 ,
  • 腫瘍細胞における細胞内Ca2+濃度上昇反応について, 和田哲幸, 羽賀景子, 池原茉理, 山田愛, 吉田泰介, 豊山舞佳, 川口明範, 浅野肇, 坂本大和, 若木千幸, 三好梨左, 飯田拓真, 船上仁範, 吉田繁, 市田成志, 日本薬学会年会要旨集, 132nd, 3, 199,   2012 03 05 ,
  • 環境ストレスによって引き起こされるマウス橋・延髄領域のc‐Fos発現の分布およびその変化, 船上仁範, 宮本朋佳, 飯田拓真, 岸孝行, 谷口友梨, 豊田和, 岸本茉希, 大浦沙貴子, 岡部由季, 川口明範, 浅野肇, 若木千幸, 三好梨左, 長野護, 重吉康史, 市田成志, 日本薬学会年会要旨集, 132nd, 3, 209,   2012 03 05 ,
  • 調剤過誤シナリオを使用した模擬患者対応ロールプレイ実習―アドバンスコミュニケーション学習―, 小竹武, 細見光一, 大鳥徹, 井上知美, 安原智久, 北小路学, 船上仁範, 谷野公俊, 村上悦子, 八軒浩子, 高田充隆, 松山賢治, 日本医療薬学会年会講演要旨集, 21st, 386,   2011 09 09 ,
  • NG108‐15細胞のcoline acetyltransferase発現に関する細胞内シグナルについて, 若木千幸, 山本達也, 中尾真理子, 川口明範, 浅野肇, 宮本朋佳, 渡辺瑞貴, 三好梨左, 飯田拓真, 船上仁範, 和田哲幸, 市田成志, 日本薬学会年会要旨集, 131st, 3, 136,   2011 03 05 ,
  • NG108‐15細胞の神経分化における,5‐HTによって引き起こされた細胞内Ca2+濃度上昇反応の性質について, 三好梨左, 川口明範, 浅野肇, 宮本朋佳, 中尾真理子, 渡辺瑞貴, 若木千幸, 飯田拓真, 船上仁範, 和田哲幸, 吉田繁, 市田成志, 日本薬学会年会要旨集, 131st, 3, 165,   2011 03 05 ,
  • 寒冷刺激の反復による橋・延髄領域の神経活性への影響, 宮本朋佳, 飯田拓真, 岸孝之, 若木千幸, 三好梨左, 川口明範, 浅野肇, 中尾真理子, 渡辺瑞貴, 船上仁範, 長野護, 和田哲幸, 重吉康文, 市田成志, 日本薬学会年会要旨集, 131st, 3, 154,   2011 03 05 ,
  • 急激な環境温度変化が視床・視床下部におよぼす影響, 飯田拓真, 宮本朋佳, 尾鍋明子, 谷岡紗良, 川口明範, 浅野肇, 中尾真理子, 渡部瑞貴, 若木千幸, 三好梨左, 船上仁範, 長野護, 和田哲幸, 重吉康史, 市田成志, 日本薬学会年会要旨集, 131st, 3, 154,   2011 03 05 ,
  • 脳虚血モデルラットにおけるシロスタゾール・ナノ粒子分散液の脳血流改善効果, 村尾卓俊, 南部義徳, 井上晃博, 長井紀章, 伊藤吉將, 船上仁範, 市田成志, 岡本紀夫, 松山知弘, 日本薬学会年会要旨集, 131st, 4, 189,   2011 03 05 ,
  • 近畿大学薬学部における模擬患者養成の取り組み, 大島徹, 木村健, 安原智久, 北小路学, 船上仁範, 石渡俊二, 谷野公俊, 村上悦子, 八軒浩子, 高田充隆, 日本薬学会年会要旨集, 130th, 4, 334,   2010 03 05 ,
  • クモ毒NPTX‐594のCa2+透過性グルタミン酸受容体に対する阻害効果について, 和田哲幸, 西丸貴弘, 和田祥子, 渡辺瑞貴, 宮本朋桂, 中尾真理子, 阪本大和, 船上仁範, 森山隆太郎, 若宮建昭, 西澤幹雄, 伊藤誠二, 吉田繁, 市田成志, 日本薬学会年会要旨集, 130th, 3, 146,   2010 03 05 ,
  • Cilostazolナノ粒子分散液の静脈内投与の検討, 村尾卓俊, 長井紀章, 伊藤吉將, 岡本紀夫, 船上仁範, 市田成志, 日本薬学会年会要旨集, 130th, 4, 188,   2010 03 05 ,
  • チーム基盤型学習(TBL)を導入した薬学部・医学部連携教育, 木村健, 安原智久, 船上仁範, 長井紀章, 喜多綾子, 北小路学, 大鳥徹, 岩城正宏, 松尾理, 日本薬学会年会要旨集, 130th, 4, 334,   2010 03 05 ,
  • NG108‐15細胞のBt2cAMP処理による神経突起伸長に対する各種シグナル阻害剤の効果およびERK‐リン酸量の変化, 若木千幸, 山本達也, 宮本朋佳, 和田祥子, 中尾真理子, 渡辺瑞貴, 川口明範, 阪本大和, 船上仁範, 和田哲幸, 市田成志, 生化学, ROMBUNNO.2P-721,   2009 09 25 ,
  • NG108‐15細胞の神経分化過程における5‐HT3受容体を介した反応性の変化, 和田祥子, 和田哲幸, 渡辺瑞貴, 川口明範, 阪本大和, 宮本朋佳, 中尾真理子, 船上仁範, 吉田繁, 市田成志, 生化学, ROMBUNNO.3P-790,   2009 09 25 ,
  • Stress-induced Hypotension and Orthostatic Hypotension in Rats, Hata Taeko, Funakami Yoshinori, Itoh Eiji, Japanese Journal of Psychosomatic Medicine, 47, 7, 607, 616,   2007 07 01 , 10.15064/jjpm.47.7_607,
    Summary:Various kinds of stress affect our health in the mind and body. In this paper, hypotension and orthostatic hypotension(OH), especially influence of stress on OH are introduced. Differing from acute stress-induced hypertension, SART(specific alternation of rhythm in temperature) stress, a kind of repeated cold stress, causes hypotension in experimental animals. The stressed animals are in a state of autonomic imbalance. OH is easily and highly elicited under the stress by postural change. Four types of OH observed in the stressed rats resemble the types of OH observed on human in the patterns of blood pressure change. The OH was improved by treatment with muscarinic M_2 receptor antagonists differently from M_1 antagonists with no or anti effects. These results show that manifestation of the SART stress-induced OH is associated greatly with parasympathetic nerve, and that the SART-stressed rats are useful for elucidation of a mechanism of OH, and development of medication.
  • SARTストレスラットにおける起立性低血症の薬物による緩解, 船上仁範, 伊藤栄次, 秦多惠子, 日本薬学会年会要旨集, 127th, 2, 138,   2007 03 05 ,
  • 保険薬局および病院実務実習に対する学生の意識調査, 北小路学, 石渡俊二, 大床真美子, 船上仁範, 八軒浩子, 多賀淳, 八木秀樹, 和田哲幸, 田邊元三, 市田成志, 西田升三, 社会薬学, 25, 2, 34,   2007 02 28 ,
  • SARTストレスラットにおける体位変換による起立性低血圧に及ぼすβ受容体遮断薬の影響, 船上仁範, 伊藤栄次, 秦多恵子, 日本薬理学雑誌, 126, 4, 16P,   2005 10 01 ,
  • 反復低温(SART)ストレスラットの起立性低血圧の実験動物モデルとしての可能性(An Experimental Animal Model for Orthostatic Hypotension: Repeatedly Cold-Stressed Rats with Autonomic Imbalance), 秦 多惠子, 船上 仁範, 伊藤 栄次, 心身医学, 45, 9, 697, 706,   2005 09 , 10.15064/jjpm.45.9_697
    Summary:反復低温負荷により作製され,vagotonia型自律神経失調症のモデル動物であり,低血圧・頻脈状態にあるSART(specific alternation of rhythm in temperature)ストレスラットを用いて,ストレスと起立性低血圧の関係をHead-up tilt試験により調べた.SARTストレスラットでは麻酔下でも意識下と同様,収縮期,拡張期血圧ともに低く,心拍数の多いことが認められた.このラットを麻酔下で背位固定し,急速に水平位から頭部を上昇し60°傾斜にする体位変換刺激を与えて低血圧を起こし,その状態を4分間持続した.このときにみられる血圧変化から,3つの指標を算出して,起立性低血圧の程度を正常ラット(非ストレス群)と比較した.SARTストレス群では,起立(60°head-up)による血圧の最大低下値が大きく,血圧上昇の反射率は有意に小さく,時間-血圧曲線-基線下面積は有意に大きかった.起立後の心拍数は非ストレス群では直後から増大したが,SARTストレス群では変化しないか,逆に減少した.このようにSARTストレスラットは体位変換によって容易にかつ重篤な起立性低血圧を惹起することが認められた.このような結果から,SARTストレスラットは起立性低血圧の実験動物モデルとしての有用な可能性を秘めていると考えられる(著者抄録)
  • ストレスラットを用いた起立性低血圧の動物モデル, 船上 仁範, 秦 多惠子, 伊藤 栄次, 日本薬理学雑誌, 121, 3, 40P, 40P,   2003 03
  • SARTストレス動物の痛覚過敏機構におけるブラディキニンの関与, 秦 多惠子, 伊藤 栄次, 桃谷 圭一, 船上 仁範, 河原井 智子, 日本薬理学雑誌, 120, 4, 18P, 18P,   2002 10
  • SARTストレスラットにおける起立性低血圧へのムスカリン受容体の関与とAF-DX116の効果, 秦 多恵子, 伊藤 栄次, 船上 仁範, 西村 知恭, 渡邉 章子, 日本薬理学雑誌, 113, 3, 51P, 51P,   1999 03

Research Grants & Projects

  • Ministry of Education, Culture, Sports, Science and Technology, Grants-in-Aid for Scientific Research(若手研究(B)), A basic research in relation to stress and hypotension, The SART (specific alternation of rhythm in temperature)-stressed rat, which is a model animal of autonomic imbalance, is associated with low blood pressure and tachycardia under both consciousness and anesthesia. Additionally, orthostatic hypotension (OH) is developed easily by postural manipulation of SART-stressed rats. Accordingly, we studied the influence of the adrenalin α1 receptor agonist phenylephrine on stress-induced OH. In SART-stressed rats, prolonged intravenous administration of phenylephrine reduced OH. Sympathetic dysfunction is suggested to be a factor underlying SART stress-induced OH.