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Pharmacological studies on central nervous control systems in gastric acid secretion and on their signal tranduction systems.

Research Project

Project/Area Number 63480461
Research Category

Grant-in-Aid for General Scientific Research (B)

Allocation TypeSingle-year Grants
Research Field Biological pharmacy
Research InstitutionChiba University

Principal Investigator

WATANABE Kazuo  Chiba Univ. Facul. of Pharmaceut. Sci., Professor, 薬学部, 教授 (80019124)

Co-Investigator(Kenkyū-buntansha) YANO Shingo  Chiba Univ. Facult. of Pharmaceut. Sci., Associate Professor, 薬学部, 助教授 (90009655)
Project Period (FY) 1988 – 1989
Project Status Completed (Fiscal Year 1989)
Budget Amount *help
¥4,300,000 (Direct Cost: ¥4,300,000)
Fiscal Year 1989: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1988: ¥2,800,000 (Direct Cost: ¥2,800,000)
KeywordsCentral Nervous System / Gastric Acid Secretion / Appetite / Gamma-amino-butyric acid / Drugs for Brain Insufficiency / Opiodes / Glutamic Acid / Receptor / GABA / ペントバルビタール / オビオイドペプチド / レセプター
Research Abstract

Central nervous control systems and their signal transduction systems in gastric acid secretion were investigated in relation to appetite control and gastric ulcer therapy on the basis of pharmacology.
In relation to brain-gut interaction, the effect of an appetite control substance, calcitonin was studied. A remarkable depressive effect of calcitonin on gastric secretion via central mechanisms was found. Close interaction with central serotonergic mechanisms with the action of calcitonin was confirmed similar to the inhibitory effect of morphine on gastric acid secretion.
In the course of the present study, we occasionally found that a general anesthetic, pentobarbital has a strong stimulatory effect on gastric acid secretion in the urethan anesthetized rats. In the mechanism of action of pentobarbital, the important contribution of central GABA mechanism was found.
In our previous study, TRH and GABA were found to stimulate gastric acid secretion which are used as the brain insufficienc … More y improver. In this connection, the effects of several drugs used for cerebral insufficiency were investigated on gastric acid secretion. Hopantenate Ca^<2+>, gamma-amino-beta-hydroxy butyrate and citicholine were found to possess distinctive stimulatory effects on gastric acid secretion. From the present results, a possibility was suggested that, in some aspect, brain metabolic state may reflect on gastric acid secretion.
In relation to GABA, we investigated the effect of some glutamate agonists on gastric secretion. A remarkable stimulatory effect of kainic acid was found as well as weak effects of glutamic acid and NMDA, but not of quisqualate. These quite novel findings will stimulate further investigation in this field. We found the strong inhibitory effect of several tricyclic antidepressant related compounds on gastric acid secretion. In addition to the above mentioned results, we succeeded to device new gastric ulcer models for the brain-gut imbalance diseases.
In total, our research project plan was successfully achieved. Less

Report

(3 results)
  • 1989 Annual Research Report   Final Research Report Summary
  • 1988 Annual Research Report
  • Research Products

    (47 results)

All Other

All Publications (47 results)

  • [Publications] W.C.Lin: "Possible involvement of the central GABA-ergic system in pento-barbital-stimulated gastric acid secretion in the rat perfused stomach preparation." Europ.J.Pharmacol.149. 33-39 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] W.C.Lin: "Stimulation of gastric acid secretion by microinjection of pento-barbital into the venteromedial hypothalamus." Res.Comm.Chem.Pathol.Pharmacol.60. 269-272 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] K.Watanabe: "Pharmacological activity of yeast extracts:Effect on GIT smooth muscles and on experimental gastric lesions.(in Japanese)" Pharmacometrics. 35. 351-357 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] S.Yano: "Effect of pentobarbital on gastric acid secretion elicited by secret-agogues or electrical vagal stimulation in rats." Japan.J.Pharmacol.49. 662-668 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] W.C.Lin: "Inhibitory effect of intravenous GABA antagonists on gastric acid secretion stimulated by secretagogues in rats." Japan.J.Pharmacol.49. 267-274 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Y.Kimura: "Involvement of metabolites in the inhibitory effects of 2-(4-ethyll-peperazinyl)-4-phenylquinolinoline dimaleate(AD-2646),a new quinoline derivative, on gastric acid secretion.A comparison with tricyclic antidepressants." J.Pharmacobio-dyn.12. 43-49 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] S.Yano: "Antiulcer activities of glycyrrhetinic acid derivatives in experi-mental gastric lesion models." Chem.Pharm.Bull.37. 2500-2504 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] K.Hatakeyama: "Platelet activating g factor(PAF)-induced gastric mucosal damage in rats;Participation of increased gastric vascular permeability." Scand.J.Gastroenterol.24,(suppl.162). 71-74 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] K.Watanabe: "Effects of carbenoxolone and prostaglandin E_2 on transgastric mucosal potential digfference in the rat stomach." Scand.J.Gastroenterol.24,(suppl.162). 87-90 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] K.Yogo: "Vasoconstrictor effect of endothelin in isolated perfused stomach of the rat in comparison with noradrenaline and serotonin." Japan.J.Pharmacol.52. 160-163 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] S.Yano: "Centrally mediated inhibitory effect of 5-(2-diethylamino)ethyl)-amino-5,ll-dihydro(1)benzoxepino-(3,4b)pyridine trihydrochloride(KW-5805)on gastric acid secretion in rats." Japan.J.Pharmacol.52. 287-293 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] S.Yano: "Stimulatory effect of some therapeutic drugs used for improving cerebral insufficiency on gastric acid secretion in rats" Pharmacology(in press). (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] K.Watanabe: "Trends in Pharmacological Research on Platelet Activating Factor(PAF)in Japan---Formation of gastric mucosal lesions by platelet acti-vating factor(PAF)Comparison of the effects of drugs on gastric lesion induced by hypovolumic shock and PAF" Ishiyaku EuroAmerica,Inc., 170-181 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] 渡辺和夫: "臨床生理学シリ-ズ「胃」:粘膜防御薬" 南江堂, 211-219 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] 渡辺和夫: "PAF(血小板活性化因子)-PAFの病態生理学的役割-消化管系" 最新医学社, 501-504 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] 渡辺和夫: "Peceptor(消化管関連ペプチド)" 日本臨床社, 1312-1316 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] W.C. LIN: "Stimulation of gastric acid secretion by microinjection of pentobarbital into the ventromedial hypothalamus." Res. Com. Chem. Pathol. Pharmacol. 60, 269-272 (1988).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] K. WATANABE: "Pharmacological activity of yeast extracts: Effect on GIT smooth muscles and on experimental lesions." Pharmacometrics, 35, 351-357 (1988).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] S. YANO: "Effect of pentobarbital on gastric acid secretion elicited by secretagogues or electrical vagal stimulation in rats." J. Pharmacobio-Dyn., 11, 662-668 (1988).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] W.C. LIN: "Inhibitory effect of intravenous GABA antagonists on gastric acid secretion stimulated by secretagogues in rats." Japan. J. Pharmacol., 49, 267-274 (1989).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Y. KIMURA: "Involvement of metabolites in the inhibitory effects of 2-(4-ethyl-1-piperazinyl)-4-phenylquinoline dimaleate (AD-2646), a new quinoline derivative, on gastric acid secretion. A comparison with tricyclic antidepressants." J. Pharmacobio-Dyn., 12, 43-49 (1989).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] S. YANO: "Antiulcer activities of glycyrrhetinic acid derivatives in experimental gastric lesion models." Chem. Pharm. Bull., 37, 2500-2504 (1989).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] K. HATAKEYAMA: "Platelet activating factor (PAF)-induced gastric damage in rats: Participation of increased gastric vascular permeability." Scand. J. Gastroenterol., 24 (Supple. 162), 71-74 (1989).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] K. WATANABE: "Effects of carbenoxolone and prostaglandin E2 on transmucosal potential difference in the rat stomach." Scand. J. Gastroenterol., 24 (Supple. 162), 87-90 (1989).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] K. YOGO: "Vasoconstrictor effect of endothelin in isolated perfused stomach of the rat in comparison with noradrenaline and serotonin." Japan. J. Pharmacol., 52, 160-163 (1990).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] S. YANO: "Centrally mediated inhibitory effect of 5-[2-(diethylamino)ethyl]-amino-5,11-dihydro[1]benzoxepino[3,4-b]pyridine trihydrochloride (KW-5805) on gastric acid secretion in rats." Japan. J. Pharmacol., 52.287-293 (1990).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] S. YANO: "Stimulatory effect of some therapeutic drugs used for improving cerebral insufficiency on gastric acid secretion in rats." Pharmacology (1990).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] S. YANO: "Increasing effects of KT-1-32, a novel antiulcer agent, on gastric mucosal blood flow in anesthetized rats."

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] K. WATANABE: "Formation of gastric mucosal lesions by platelet activating factor (PAF): Comparison of the effects of drugs on gastric lesions induced by hypovolumic shock and PAF. In Trends in Pharmacological Research on Platelet Activating Factor (PAF) in Japan." Ishiyaku EuroAmerica, Inc. pp 170-181 (1988).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] K. WATANABE: "Drugs for promoting mucosal defensive mechanisms. In Series of Clinical Physilogy III -Stomach-. (in Japanese)" Nankoudou, Inc. pp 211-219 (1988).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] W.C.Lin: "Inhibitory effect of intravenous GABA antagonists on gastric acid secretion stimulated by secretagogues in rats." Japan.J.Pharmacol.49. 267-274 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] Y.Kimura: "Involvement of metabolites in the inhibitory effects of 2-(4-ethyl-l-peperazinyl)-4-phenylquinoline dimaleate(AD-2646),a new quinoline derivative,on gastric acid secretion.A comparison with tricyclic antidepressants." J.Pharmacobio-dyn.12. 43-49 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] S.Yano: "Antiulcer activities of glycyrrhetinic acid derivatives in experimental gastric lesion models." Chem.Pharm.Bull.37. 2500-2504 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] K.Hatakeyama: "Platelet activating factor(PAF)-induced gastric damage in rats:Participation of increased gastric vascular permeability." Scand.J.Gastroenterol.24(suppl.162). 71-74 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] K.Watanabe: "Effects of carbenoxolone and prostaglandin E_2 on transmucosal potential deference in the rat stomach." Scand.J.Gastroenterol.24(suppl.162). 87-90 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] K.Yogo: "Vasoconstrictor effect of endothelin in isolated perfused stomach of the rat in comparison with noradrenaline and serotonin." Japan.J.Pharmacol.52. 160-163 (1990)

    • Related Report
      1989 Annual Research Report
  • [Publications] S.Yano: "Centrally mediated inhibitory effect of 5-(2-(diethylamino)ethyl)-amino-5,11-dihydro(1)benzoxepino(3,4-b)pyridine trihydrochloride(KW-5805)on gastric acid secretion in rats." Japan.J.Pharmacol.52. 287-293 (1990)

    • Related Report
      1989 Annual Research Report
  • [Publications] S.Yano: "Stimulatory effect of some therapeutic drugs used for improving cerebral insufficiency on gastric acid secretion in rats." Pharmacology.

    • Related Report
      1989 Annual Research Report
  • [Publications] 渡辺和夫: "Receptor(消化管関連ペプチド)(分担執筆)" 日本臨床, 1312-1316 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] 渡辺和夫: "血小板活性化因子-生化学、生理、病理-(潰瘍)(分担執筆)" 198-203 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] Wen C,Lin: Europ.J.Pharmacol.149. 33-39 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] Shingo,Yano: J.Pharmacobio-dyn.11. 662-668 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] Wen C,Lin: Japan.J.Pharmacol.49. 267-274 (1989)

    • Related Report
      1988 Annual Research Report
  • [Publications] Wen C,Lin: Res.Comm.Chem.Path.pharmacol.60. 269-272 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] Yuka,Kimura: J.Pharmacobio-dyn.12. 43-49 (1989)

    • Related Report
      1988 Annual Research Report
  • [Publications] Kazuo,Watanabe: Europ.J.Pharmacol.

    • Related Report
      1988 Annual Research Report
  • [Publications] Kazuo,Watanabe: "Trends in Pharmacological Research on Platelet Activating Factor(PAF)in Japan" Ishiyaku EuroAmerica, 170-181 (1988)

    • Related Report
      1988 Annual Research Report

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Published: 1988-04-01   Modified: 2016-04-21  

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