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Peripheral and central involvement of 5-hydroxytryptamine in control of interdigestive migrating contractions by motilin.

Research Project

Project/Area Number 04454239
Research Category

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

Allocation TypeSingle-year Grants
Research Field Gastroenterology
Research InstitutionGunma Univ.

Principal Investigator

ITOH Susumu  Gunma Univ., Institute of Endocrinology, Professor, 内分泌研究所, 教授 (00008294)

Co-Investigator(Kenkyū-buntansha) SAKAI Takafumi  Gunma Univ., Institute of Endocrinology, Research Associate, 内分泌研究所, 助手 (40235114)
Project Period (FY) 1992 – 1993
Project Status Completed (Fiscal Year 1993)
Budget Amount *help
¥6,000,000 (Direct Cost: ¥6,000,000)
Fiscal Year 1993: ¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1992: ¥3,900,000 (Direct Cost: ¥3,900,000)
KeywordsMotilin / Interdigestive migrating complex / Serotonin
Research Abstract

1. In order to study the role 5-hydroxytryptamine in the peripheral action of motilin, the canine stomach was perfused with artificial blood after the stomach was isolated from the donor dog. As a result, motilininduced contractions migrated toward the pyloric ring in the isolated stomach were completely inhibited by treatment of the perfused stomach with a 5-hydroxytryptamine 3 receptor antagonist. It is concluded that 5-hydroxytryptamine is involved in the action of motilin in the isolated stomach. In the same system, it was also found that alpha-adrenergic receptors and the cholinergic neuron were involved in the action of motilin.
2. The effects of various receptor antagonists on EM523-induced contractions in the gastrointestinal tract were studied in conscious dogs in which force trasducers were chronically implanted to measure gastrointestinal contractions. EM523, a non-peptide motilin agonist, was found to induce phase III-like contractions in the stomach in a dose-related manner with concomitant increase in the plasma consentration of motilin. The EM523-induced contractions in the stomach were eliminated by pretreatment of dogs with cholinergic and 5-hydroxytryptamine 3 receptor antagonists, and dopamine, but the contractions were not influenced by opiate (mu) receptor antagonist and methysergide. These findings obtained in conscious dogs agree with those found in the isolated stomach.
3 In the present study, it was revealed that 5-hydroxytryptamine neuron is involved in the control of contractions in the gastrointestinal tract by motilin, but the relationship between 5-hydroxytryptamine neuron and motilin receptors in the stomach has not been elucidated ; this should be clarified in the future. The role of 5-hydroxytryptamine in the CNS in the control of the interdigestive migrating contractions by motilin has been also studied, but no definite conclusion could be obtained ; further studies are needed.

Report

(3 results)
  • 1993 Annual Research Report   Final Research Report Summary
  • 1992 Annual Research Report
  • Research Products

    (38 results)

All Other

All Publications (38 results)

  • [Publications] Mizumoto,A.: "Endogenous CCK is not involved in the ragulation of interdigestive gastrointestinal and gallbladder motility in conscious dogs" Regul.Pept.41. 249-256 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Mizumoto,A.: "Pituitary adenylate cyclase activating polypeptide stimulates gallbladder motility in conscious dogs" Regul.Pept.42. 39-50 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Shibata,C.: "Characterization of colonic motor activity in couscious dogs" J.Gastrointest.Mot.5. 9-16 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Ohtawa,M.: "Mechanism of gastrokinetic effect of EM523,an erythromycin derivative,in dogs" Gastroenterology. 104. 1320-1327 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Kawamura,O.: "Effect of erythromycin on interdigestive gastrointestinal contractile activiry and plasma concentration in humans" Dig.Dis.Sci.38. 870-876 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Kuwahara,O.: "Effect of erythromycin derivative EM523L on human interdigestive gastrointestinal tract." Dig.Dis.Sci.38. 1026-1031 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Ueki,S.: "Gastrokinetic activity of nizatidine,a new H2-receptor antagonist,and its possible mechanism of action in dogs and rats." J.Pharmacol.Exp.Ther.264. 152-157 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Mlzumoto,A.: "Mechanism of motilin-induced contractions in isolated perfused canie stomach." Gastroenterology. 105. 425-432 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Inatomi,N.: "Comparison of the Motor-Stimulating Action of EM523,an Erythromycin Derivative,and Prostaglandin F2α in Conscous Dogs" Japan.J.Pharmacol.63. 209-217 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Sakai,T.: "Biotynil C-terminal-extended motilin as a biologicvally active receptor probe." PEPTIDES. 15. 257-262 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Sakai,T.: "Localization of motilin-immunopositive cells in the rat intestine by light microscopoic immunocytochemistry" PEPTIDES. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Mizumoto, A., Ueki, S., Ohtawa, M., Itoh, Z.: "Endogenous CCK is not involved in the regulation of interdigestive gastrointestinal and gallbladder motility in conscious dogs." Regulatory Peptides. 41. 249-256 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Mizumoto, A., Fujimura, M., Ohtawa, M., Ueki, S., Itoh, Z., Fujino, M., Arimura, A.: "Pituitary adenylate cyclase activating polypeptide stimulates gallbladder motility in conscious dogs." Regulatory Peptides. 42. 39-50 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Shibata, C., Sasaki, I., Matsuno, S., Mizumoto, A., Iwanaga, Y., Itoh, Z: "Characterization of colonic motor activity in conscious dogs." J.Gastrointest. Mot.5. 9-16 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Ohtawa, M., Mizumoto, A., Hayashi, N., Yanagida, K., Itoh, Z., Omura, S.: Gastroenterology. 104. 1320-1327 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Kawamura, O., Sekiguchi, T., Kusano, M., Nishida, T., Itoh, Z.: "Effect of erythromycin on interdigestive gastrointestinal contractile activity and plasma motilin concentraiton in humans." Digestive Diseases and Sciences. 38. 870-876 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Kawamura, O., Sekiguchi, T., Itoh, Z., Omura, S.: "Effect of erythromycin derivative EM523L on human interdigestive gastrointestinal tract." Digestive Diseases and Sciences. 38. 1026-1031 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Ueki, S., Seiki, M., Yoneta, T., Aita, H., Chaki, K., Hori, Y., Morita, H., Tagashira, E., Itoh, Z.: "Gastrokinetic activity of Nizatidine, a new H2-receptor antagonist, and its possible mechanism of action in dogs and rats." J.Pharmacol. Exp.Ther.264. 152-157 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Mizumoto, A., Sano, I., Matsunaga, Y., Yamamoto, O., Itoh, Z., Ohshima, K.: "Mechanism of motilin-induced contractions in isolated perfused canine stomach." Gastroenterology. 105. 425-432 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Inatomi, N., Satoh, T., Satoh, H., Itoh, Z., Omura, S.: "Comparison of the moter-stimulating action of EM523, an erythromycin derivative, and prostaglandin F2alpha in conscious dogs." Japan.J.Pharmacol. 63. 209-217 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Sakai, T., Satoh, M., Hayashi, H., Fujikura, K., Sano, I., Koyama, H., Tatemoto, K., Itoh, Z.: "Biotinyl C-terminal-extended motilin as a biologically active receptor probe" PEPTIDES. 15. 257-262 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Sakai, T., Satoh, M., Koyama, H., Iesaki, K., Umahara, M., Fujikura, K., Itoh, Z.: "Localization of motilin-immunopositive cells in the rat intestine by light microscopic immunocytochemistry" PEPTIDES. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Mizumoto,A.: "Mechanism of motilin-induced contractions in isolated perfused canie stomach." Gastroenterology. 105. 425-432 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Ohtawa,M.: "Mechanism of gastrokinetic effect of EM523,an erythromycin derivative,in dogs" Gastroenterology. 104. 1320-1327 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Kawamura,O.: "Effect of erythromycin on interdigestive gastrointestinal contractile activiry and plasma concentration in humans" Dig.Dis.Sci.38. 870-876 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Kuwahara,O.: "Effect of erythromycin derivative EM523L on human interdigestive gastrointestinal tract." Dig.Dis.Sci.38. 1026-1031 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Ueki,S.: "Gastrokinetic activity of nizatidine,a new H2-receptor antagonist,and its possible mechanism of action in dogs and rats." J.Pharmacol.Exp.Ther.264. 152-157 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Sakai,T.: "Biotynil C-terminal-extended motilin as a biologicvally active receptor probe." PEPTIDES.

    • Related Report
      1993 Annual Research Report
  • [Publications] Inatomi,N.: "Comparison of the motor-stimulating action of EM523,an erythromycin derivative,and prostaglandin F2α in conscious dogs." Japan J.Pharmacol.63. 209-217 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Sakai,T.: "EM574,one of the motilides acts as a motilin agonist on human stomach motilin receptors:in vitro demonstrations." J.Gastrointest.Mot.5. 214 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Itoh Z: "Discovery and development of motilin agonist in nonpeptide substance." Regulatory Peptides. 40. 174 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Mizumoto A: "Endogenous CCK is not involved in the regulation of interdigestive gastrointestinal and gallbladder motility in conscious dogs." Regulatory Peptides. 41. 249-256 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Inatomi N: "Mechanism of the motor-stimulating action of motility and motilide (EM574)in the dog." Regulatory Peptides. 40. 172 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Mizumoto A: "Pituitary adenylase cyclase activating polypeptide stimulates gallbladder motility in concscious dogs." Regulatory Peptides. 42. 39-50 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Miyashita N: "A novel specific 5-Hydroxytryptamine receptor (5-HT4)agonist in gastrointestinal motility." Gastroenterology. 102. A488 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Ohtawa M: "Pharmacological characterization of canine gastric contractions induced by EM523,Erythromycin derivative." Gastroenterology. 102. A495 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] 水本 明良: "H2受容体拮抗剤の諸作用とその問題点、医学図書出版" 意識下犬のコリンエステラーゼ活性にぼすH2受容体拮抗剤の影響, 7 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] 林 直樹: "H2受容体拮抗剤の諸作用とその問題点、医学図書出版" 空腹期収縮に対するH2受容体拮抗剤の作用, 8 (1992)

    • Related Report
      1992 Annual Research Report

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Published: 1992-04-01   Modified: 2016-04-21  

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