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Mechanisms of action of cholecystokinin in the canine gastrointestinal tract: role of vasoactive intestinal peptide and nitric oxide.
Vergara, P; Woskowska, Z; Cipris, S; Fox-Threlkeld, J E; Daniel, E E.
Afiliação
  • Vergara P; Department of Biomedical Sciences, McMaster University, Faculty of Health Sciences, Hamilton, Ontario, Canada.
J Pharmacol Exp Ther ; 279(1): 306-16, 1996 Oct.
Article em En | MEDLINE | ID: mdl-8859008
ABSTRACT
This study defined the cholecystokinin (CCK)/gastrin receptor subtypes at which CCK octapeptide (CCK8) and gastrin 17 (G17)act on motor functions of the intact canine gastrointestinal tract. In the antrum, studies of tachyphylaxis and effects of antagonists showed that i.a. G17 acted through CCKB receptors to activate contractions, whereas CCK8 acted through A and B receptor subtypes to produce contractions. In the duodenum, i.a. G17 caused dose-dependent inhibition of electrical field-stimulated contractions, apparently by release of nitric oxide [blocked by N-nitro-L-arginine (L-NNA) or NG-L-arginine methyl ester]. These inhibitory effects were abolished by YM022 (a CCKB antagonist) but not by L-364, 718 (a CCKA antagonist). However, i.a. CCK8 increased electrical field-stimulated contractions and L-364, 718 reversed this effect. In isolated perfused segments of distal intestine, CCK8 caused inhibition and excitation and released vasoactive intestinal peptide (VIP) into the venous effluent. CCK tetrapeptide and G17 had inconsistent effects. Excitation and VIP release were inhibited by L-364, 718. L-NNA potentiated excitatory responses and abolished inhibitory responses. Tetrodotoxin and atropine abolished and hexamethonium reduced excitatory responses to CCK8, but L-NNA restored contractions after atropine treatment. Hexamethonium or L-NNA (but not atropine) reduced VIP release; CCK8 still enhanced it. L-364, 718 abolished hexamethonium-resistant contractions and VIP release. Thus, CCK/gastrin peptides act on neural receptors in intact canine gastrointestinal tract. In antrum, activation of neural CCKA or CCKB receptors initiates contractions. In intestine, CCKA receptors at pre- and postjunctional sites in enteric nerves mediate acetylcholine and VIP release. CCKB receptors mediate release of an inhibitory mediator, apparently nitric oxide, from postjunctional sites.
Assuntos
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Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Colecistocinina / Peptídeo Intestinal Vasoativo / Motilidade Gastrointestinal / Óxido Nítrico Limite: Animals Idioma: En Revista: J Pharmacol Exp Ther Ano de publicação: 1996 Tipo de documento: Article País de afiliação: Canadá
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Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Colecistocinina / Peptídeo Intestinal Vasoativo / Motilidade Gastrointestinal / Óxido Nítrico Limite: Animals Idioma: En Revista: J Pharmacol Exp Ther Ano de publicação: 1996 Tipo de documento: Article País de afiliação: Canadá