REGULATION OF GASTRIN, SOMATOSTATIN AND BOMBESIN RELEASE FROM THE ISOLATED RAT STOMACH BY EXOGENOUS AND ENDOGENOUS GAMMA-AMINOBUTYRIC-ACID

Background/Aims and Methods: gamma-Aminobutyric acid (GABA) is localiz ed in epithelial cells and intrinsic nerve fibers of the gastric mucos a raising the possibility of a regulatory role for this transmitter. T herefore, it was the aim of the present study to examine the effect of exogenous and endogenous GABA on the neuroendocrine functions of the isolated perfused rat stomach. Results: Infusion of GABA (10(-8), 10(- 6), 10(-4) M) caused a significant increase in gastrin release by 187 +/- 98, 328 +/- 43 and 493 +/- 84 pg/20 min and a significant decrease in somatostatin secretion by -540 +/- 203, -867 +/- 96 and -893 +/- 1 95 pg/20 min, respectively. Release of bombesin-like immunoreactivity (BLI) remained unchanged during infusion of GABA at the concentrations employed. The gastrin and somatostatin responses to 10(-4) M GABA wer e completely inhibited by the GABAA antagonist bicuculline (10(-5) M) and the cholinergic blocker atropine (10(-7) M), whereas the GABA(B) a ntagonist CGP 35 348 (5 x 10(-5) M) was ineffective. To evaluate the c ontribution of endogenous GABA in the vagal regulation of gastric neur oendocrine functions, gastrin, somatostatin and BLI responses to elect rical stimulation of the vagal nerves were examined in the presence of bicuculline. Vagal stimulation (10 V, 10 Hz, 1 ms) induced a signific ant inhibition of somatostatin release by -518 +/- 78 pg/10 min, which was attenuated to -259 +/- 143 pg/10 min (p < 0.05) in the presence o f bicuculline. Atropine (10(-7) M) turned vagally induced inhibition o f somatostatin release into a stimulation by 928 +/- 266 pg/10 min whi ch was not altered by additionally infused bicuculline. Vagally stimul ated gastrin release was reduced from 397 +/- 47 to 217 +/- 72 pg/10 m in (p < 0.05) by bicuculline, while atropine had no effect. Vagally in duced BLI release was not altered by bicuculline and atropine. Since t he effect of bicuculline on vagally induced gastrin release was indepe ndent of cholinergic mechanisms, a potential direct effect of GABA on gastrin release was examined in isolated rabbit antral G cells. In thi s preparation carbachol (10(-4) M) and neuromedin C (10(-9) M) signifi cantly stimulated gastrin release from 2.6 +/- 0.4 to 4.9 +/- 0.3 and 8.5 +/- 0.9% of the total cellular content, respectively, while GABA ( 10(-10)-10(-3) M) changed neither basal nor carbachol-and neuromedin C -stimulated gastrin release. Conclusion: The present data confirm that exogenous GABA stimulates gastrin release and inhibits somatostatin r elease from the isolated rat stomach via GABAA receptors by activating cholinergic neurotransmission. Furthermore, it was shown for the firs t time that endogenous GABA contributes to the vagal regulation of gas trin and somatostatin release from the rat stomach. Inhibition of soma tostatin secretion by endogenous GABA is mediated by cholinergic mecha nisms, whereas stimulation of gastrin release is mediated by pathways unrelated to the cholinergic system and bombesin peptides.