1993 Fiscal Year Final Research Report Summary
Molecular pharmacological study of receptors for enteric neurons
| Project/Area Number |
04454149
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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 |
General pharmacology
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| Research Institution | Department of Pharmacolaogy 2, Nagasaki University School of Medicine |
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Principal Investigator |
TANIYAMA Kohtaro Nagasaki University School of Medicine, Professor, 医学部, 教授 (70030898)
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| Co-Investigator(Kenkyū-buntansha) |
YAMASHITA Kimihiro Nagasaki University School of Medicine, Instractor, 医学部, 助手 (50192399)
KATAOKA Yasufumi Nagasaki University School of Medicine, Associate Professor, 医学部, 講師 (70136513)
NIWA Masami Nagasaki University School of Medicine, Associate Professor, 医学部, 助教授 (20136641)
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| Project Period (FY) |
1992 – 1993
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| Keywords | Xenopus oocytes / Vasoactive intestinal contractor / Endothelin receptor / desensitization / pertussis toxin / Ca^<2+>-activated Cl^- channel / G-protein |
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| Research Abstract |
Vasoactive intestinal contractor (VIC) is a peptide of the endothelin (ET) family which is a potent vasoactive substance, and the VIC gene is expressed in the intestine, but apprarently not in other tissues. The present study was attempted to examine the localization and properties of receptor for VIC.Application of VIC produced a transient relaxation of the isolated guinea pig small intestine followed by contraction, as in the case of ETs (ET-1, ET-2 and ET-3). VIC produced contractions by stimulating both smooth muscle cells and cholinergic neurons. The VIC-induced contraction mediated by stimulation of smooth muscle was prevented by desensitization to ETs, but the VIC-induced release of acetylcholine (ACh) was not affected by desensitization to ETs. These results indicate that VIC specific receptors, distinct from endothelin ET_A and ET_B receptors, are present in the cholinergic neurons. The functional specific receptor for VIC was expressed in Xenopus oocytes by injecting mRNA obtained from the intestine of the rat. Application of VIC induced an inward current under voltage-clamp conditions. The VIC-induced inward currents were suppressed either by the external application of intracellular Ca^<2+> chelator, or by the external concentrations of Cl^- in agreement with the Nernst equation, thereby indicating that property of the current is Ca^<2+>-activated Cl^- current. The VIC-induced currents were suppressed by pretreatment with pertussis toxin. Thus, the specific receptor for VIC, expressed in Xenopus oocytes injected with rat intestinal mRNA, functions via pertussis toxin-sensitive G-protein and Ca^<2+>-activated Cl^- channels.
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