title: Role of gastrin in bombesin-stimulated somatostatin release.
abstract: The intermediary pathways in the bombesin-induced somatostatin release were examined in isolated perfused rat stomach obtained from male rats that were fasted overnight. The stomachs were perfused by way of the celiac artery. On coinfusion of 1.0 mumol/L tetrodotoxin and 1 nmol/L bombesin, a significant depression in release of somatostatin was observed compared with that observed with bombesin alone. The 5-minute integrated somatostatin response after treatment with tetrodotoxin and bombesin was 173% +/- 14% of basal, which was significantly lower than that observed with bombesin alone (394% +/- 59% of basal, P less than 0.05) but significantly higher than that observed with medium-199 alone (95% +/- 7% of basal, P less than 0.05); this indicated that approximately 70% of the bombesin-stimulated somatostatin release was indirectly mediated through neural pathways, while a significant (approximately 30%) segment of it was mediated by nonneural mechanisms. To test if the 30% somatostatin release was secondary to gastrin release in response to bombesin, gastrin antiserum and bombesin (1 nmol/L) were coadministrated in the presence or absence of tetrodotoxin (1 mumol/L). Gastrin antiserum alone did not significantly affect basal release of somatostatin but caused a significant inhibition (approximately 23%) of bombesin-provoked somatostatin release. Coadministration of gastrin antiserum and tetrodotoxin attenuated bombesin-stimulated somatostatin release. Gastrin (1 mumol/L) alone significantly stimulated somatostatin release (150% +/- 10% of basal), which was completely attenuated in the presence of gastrin antiserum. Tetrodotoxin did not affect bombesin-elicited gastrin release, confirming that bombesin-stimulated gastrin release was directly mediated. To determine the nature of the neural pathways mediating the bombesin-induced somatostatin release, atropine (100 nmol/L) was used. Atropine inhibited bombesin-induced somatostatin release to the same extent as tetrodotoxin, indicating that cholinergic pathways mediated bombesin-induced somatostatin release. These results show that almost all the somatostatin response to bombesin is indirectly mediated, and is composed of a major neural (cholinergic) and a minor nonneural pathway. The nonneural mechanism appears to be contributed primarily by gastrin released in response to bombesin, which apparently has a short paracrine positive feedback effect on somatostatin release.
authors.affiliation: Department of Surgery, University of Texas Medical Branch, Galveston.
authors.forename: Y S
authors.initials: YS
authors.lastname: Guo
authors.forename: J C
authors.initials: JC
authors.lastname: Thompson
authors.forename: P
authors.initials: P
authors.lastname: Singh
mesh_terms: D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001839:Bombesin / Q000494:pharmacology*; D005755:Gastrins / Q000378:metabolism / Q000502:physiology*; D008297:Male; D008959:Models, Neurological; D009434:Neural Pathways / Q000187:drug effects; D051381:Rats; D013004:Somatostatin / Q000378:metabolism*; D013270:Stomach / Q000294:innervation; D013779:Tetrodotoxin / Q000494:pharmacology; D013997:Time Factors
chemical_list: D005755:Gastrins; D013779:Tetrodotoxin; D013004:Somatostatin; D001285:Atropine; D001839:Bombesin