Cholecystokinin, but not gastrin, induces gamma-aminobutyric acid release from myenteric neurons of the guinea pig ileum.
Effects of cholecystokinin (CCK) and gastrin on the release of acetylcholine (ACh) and gamma-aminobutyric acid (GABA) were examined in the longitudinal muscle with myenteric plexus (LM-MP) preparations of the guinea pig small intestine. CCK and gastrin induced the Ca++-dependent and tetrodotoxin-sensitive release of [3H]ACh from the LM-MP preparations preloaded with [3H]choline. Proglumide, but not scopolamine, hexamethonium and [D-Pro2,D-Trp7,9]substance P inhibited the release of [3H]ACh induced by CCK and gastrin. The desensitization to CCK and gastrin was observed with a 30-min exposure of the preparation to CCK and gastrin, respectively, and the cross-desensitization to peptides was not observed, thereby indicating that these peptides induce the release of ACh mainly via respective receptors. Bicuculline which inhibited completely the release of [3H]ACh induced by GABA inhibited the release of [3H]ACh induced by CCK but not by gastrin by 42.3 +/- 4.22%. CCK, but not gastrin, produced the Ca++-dependent and tetrodotoxin-sensitive release of endogenous GABA and [3H]GABA from LM-MP preparations preloaded with [3H]GABA. The release of [3H]GABA induced by CCK was antagonized by proglumide, but not by scopolamine, hexamethonium and [D-Pro2,D-Trp7,9]substance P. These results provide evidence that the GABAergic neuron is stimulated by CCK, but not by gastrin and stimulates the cholinergic neuron.
Sano
I
I
Department of Pharmacology, Kobe University School of Medicine, Japan.
Taniyama
K
K
Tanaka
C
C
D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D002766:Cholecystokinin / Q000494:pharmacology*; D005260:Female; D005755:Gastrins / Q000494:pharmacology*; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009197:Myenteric Plexus / Q000187:drug effects* / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism* / Q000494:pharmacology
D005755:Gastrins; D005680:gamma-Aminobutyric Acid; D002766:Cholecystokinin; D000109:Acetylcholine; D001640:Bicuculline