1991 Fiscal Year Final Research Report Summary
Molecular Biological Studies on the Action Mechanisms of Motilin and its Receptor
| Project/Area Number |
02454227
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Gastroenterology
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| Research Institution | Gunma University |
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Principal Investigator |
ITOH Zen Gunma Univ. Inst. of Endocrinol. Comparative Endocrinology Division Professor, 内分泌研究所・比較内分泌部門, 教授 (00008294)
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| Co-Investigator(Kenkyū-buntansha) |
KOHAMA Kazuhiro Gunma Univ. School of Medicine Dept. of Pharmacology Professor, 医学部・薬理学教室, 教授 (30101116)
KONDOH Youichi Gunma Univ. Inst. of Endocrinol. Physico-chemistry Division Professor, 内分泌研究所・物理化学部門, 教授 (70008598)
TAKEUCHI Toshiyuki Gunma Univ. Inst. of Endocrinol. Molecular Endocrinology Division Professor, 内分泌研究所・化学構造部門, 教授 (00109977)
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| Project Period (FY) |
1990 – 1991
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| Keywords | Motilin / Interdigestive migrating contraction (IMC) / Smooth muscle cell contraction |
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| Research Abstract |
Motilin is a polypeptide consisting of 22 amino acid residues and was originally isolated from the duodenal mucosa of hogs The major functions of motilin appear to be the acceleration of gastric emptying and the apparent initiation of the interdigestive migrating contractions (IMC). Rhythmic oscillations of circulating motilin levels, with peaks occuring every 90-120 min, correlate well with the appearance of phase Ill motor activity in the gastrointestinal tract. Furthermore, intravenous infusion of motilin in -concious dogs and humans during the interdigestive period initiated IMCs in the anteroduodenal region. In vivo studies demonstrate that cholinergic blockade with atropine abolished the stimulating effect of motilin in fundic and antral pouches of stomach and motilin increases IMC in denervated stomach but not denervated jejunum in dogs. Thus, both humoral and neural mechanisms have been postulated to be responsible for the action of motilin. However, the mechanism responsible f
… More
or the action of motilin on gastrointestinal motility is unclear at the cellular and molecular levels. We postulated the existence of motilin receptors on rabbit antral and duodenal smooth muscle tissues and attempted the demonstration of direct binding of ^<125>l-motilin to its receptors. The specific binding of ^<125>l-motilin to duodenal muscle slice was initially demonstrated by both its direct binding and displacement of ^<125>l-motilin by a variety of non-labeled analogues including erythromycin derivatives. However, the specific binding of ^<125>l-motilin to isolated smooth muscle membranes was not confirmed by some unknown reasons. We are currently trying to show that motilin may act through presynaptic nerve endings that may release acetylcholine or other neurotransmitters. At the same time we have prepared highly radioactive motilin ligands with substitution of methionin for leucine at position 13 and with addition of tyrosine at less bioactive sites of the motilin sequence in order to maintain highly specific binding activity. At present we are continuing the binding study of ^<125>l-motilin to rabbit antral and duodenal smooth muscle cell membranes. Less
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