Mechanisms of action of cholecystokinin in the canine gastrointestinal tract: Role of vasoactive intestinal peptide and nitric oxide

P. Vergara; Z. Woskowska; S. Cipris; J. E.T. Fox-Threlkeld; E. E. Daniel

Mechanisms of action of cholecystokinin in the canine gastrointestinal tract: Role of vasoactive intestinal peptide and nitric oxide

P. Vergara, Z. Woskowska, S. Cipris, J. E.T. Fox-Threlkeld, E. E. Daniel

Research output: Contribution to journal › Article › Research › peer-review

Abstract

This study defined the cholecystokinin (CCK)/gastrin receptor subtypes at which CCK octapeptide (CCK(B)) 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 CCK(B) receptors to activate contractions, whereas CCK(B) acted through A and B receptor subtypes to produce contractions. In the duodenum, i.a. G17 caused dose-dependent inhibition of electrical fieldstimulated 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 YMO22 (a CCK(B) antagonist) but not by L-364,718 (a CCKA antagonist). However, i.a. CCK(B) increased electrical field-stimulated contractions and L-364,718 reversed this effect. In isolated perfused segments of distal intestine, CCK(B) 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 CCK(B), but L-NNA restored contractions after atropine treatment. Hexamethonium or L-NNA (but not atropine) reduced VIP release; CCK(B) 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 CCK(A) or CCK(B) receptors initiates contractions. In intestine, CCK(A) receptors at pre- and postjunctional sites in enteric nerves mediate acetylcholine and VIP release. CCK(B) receptors mediate release of an inhibitory mediator, apparently nitric oxide, from postjunctional sites.

Original language	English
Pages (from-to)	306-316
Journal	Journal of Pharmacology and Experimental Therapeutics
Volume	279
Issue number	1
Publication status	Published - 1 Oct 1996

Cite this

@article{1160a170a1934ea9958556ad2ba16db8,

title = "Mechanisms of action of cholecystokinin in the canine gastrointestinal tract: Role of vasoactive intestinal peptide and nitric oxide",

abstract = "This study defined the cholecystokinin (CCK)/gastrin receptor subtypes at which CCK octapeptide (CCK(B)) 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 CCK(B) receptors to activate contractions, whereas CCK(B) acted through A and B receptor subtypes to produce contractions. In the duodenum, i.a. G17 caused dose-dependent inhibition of electrical fieldstimulated 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 YMO22 (a CCK(B) antagonist) but not by L-364,718 (a CCKA antagonist). However, i.a. CCK(B) increased electrical field-stimulated contractions and L-364,718 reversed this effect. In isolated perfused segments of distal intestine, CCK(B) 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 CCK(B), but L-NNA restored contractions after atropine treatment. Hexamethonium or L-NNA (but not atropine) reduced VIP release; CCK(B) 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 CCK(A) or CCK(B) receptors initiates contractions. In intestine, CCK(A) receptors at pre- and postjunctional sites in enteric nerves mediate acetylcholine and VIP release. CCK(B) receptors mediate release of an inhibitory mediator, apparently nitric oxide, from postjunctional sites.",

author = "P. Vergara and Z. Woskowska and S. Cipris and Fox-Threlkeld, {J. E.T.} and Daniel, {E. E.}",

year = "1996",

month = oct,

day = "1",

language = "English",

volume = "279",

pages = "306--316",

number = "1",

}

TY - JOUR

T1 - Mechanisms of action of cholecystokinin in the canine gastrointestinal tract: Role of vasoactive intestinal peptide and nitric oxide

AU - Vergara, P.

AU - Woskowska, Z.

AU - Cipris, S.

AU - Fox-Threlkeld, J. E.T.

AU - Daniel, E. E.

PY - 1996/10/1

Y1 - 1996/10/1

N2 - This study defined the cholecystokinin (CCK)/gastrin receptor subtypes at which CCK octapeptide (CCK(B)) 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 CCK(B) receptors to activate contractions, whereas CCK(B) acted through A and B receptor subtypes to produce contractions. In the duodenum, i.a. G17 caused dose-dependent inhibition of electrical fieldstimulated 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 YMO22 (a CCK(B) antagonist) but not by L-364,718 (a CCKA antagonist). However, i.a. CCK(B) increased electrical field-stimulated contractions and L-364,718 reversed this effect. In isolated perfused segments of distal intestine, CCK(B) 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 CCK(B), but L-NNA restored contractions after atropine treatment. Hexamethonium or L-NNA (but not atropine) reduced VIP release; CCK(B) 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 CCK(A) or CCK(B) receptors initiates contractions. In intestine, CCK(A) receptors at pre- and postjunctional sites in enteric nerves mediate acetylcholine and VIP release. CCK(B) receptors mediate release of an inhibitory mediator, apparently nitric oxide, from postjunctional sites.

AB - This study defined the cholecystokinin (CCK)/gastrin receptor subtypes at which CCK octapeptide (CCK(B)) 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 CCK(B) receptors to activate contractions, whereas CCK(B) acted through A and B receptor subtypes to produce contractions. In the duodenum, i.a. G17 caused dose-dependent inhibition of electrical fieldstimulated 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 YMO22 (a CCK(B) antagonist) but not by L-364,718 (a CCKA antagonist). However, i.a. CCK(B) increased electrical field-stimulated contractions and L-364,718 reversed this effect. In isolated perfused segments of distal intestine, CCK(B) 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 CCK(B), but L-NNA restored contractions after atropine treatment. Hexamethonium or L-NNA (but not atropine) reduced VIP release; CCK(B) 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 CCK(A) or CCK(B) receptors initiates contractions. In intestine, CCK(A) receptors at pre- and postjunctional sites in enteric nerves mediate acetylcholine and VIP release. CCK(B) receptors mediate release of an inhibitory mediator, apparently nitric oxide, from postjunctional sites.

M3 - Article

VL - 279

SP - 306

EP - 316

IS - 1

ER -

Mechanisms of action of cholecystokinin in the canine gastrointestinal tract: Role of vasoactive intestinal peptide and nitric oxide

Abstract

Fingerprint

Cite this