BOMBESIN GRP-STIMULATED SOMATOSTATIN SECRETION IS MEDIATED BY GASTRIN IN THE ANTRUM AND INTRINSIC NEURONS IN THE FUNDUS

The mechanism of action of bombesin, also known as gastrin-releasing peptide (GRP), on somatostatin secretion was examined separately in superfused segments of rat antral and fundic mucosa. Bombesin/GRP (1 nM) stimulated somatostatin secretion from both regions. In fundic segments, the somatostatin response was strongly inhibited (86%; P < 0.01) by tetrodotoxin (5-mu-M) but augmented by atropine (1-mu-M) (P < 0.01). In antral segments, both tetrodotoxin and atropine augmented the somatostatin response to bombesin/GRP by 42-45% (P < 0.01), whereas the gastrin antagonist L 365260 (1-mu-M) abolished it. The gastrin antagonist augmented the gastrin response to bombesin/GRP by 103% (P < 0.01). The results indicate that bombesin/GRP stimulates somatostatin secretion by distinct mechanisms in the fundus and antrum. In the fundus, bombesin/GRP acts indirectly on somatostatin cells by activating stimulatory noncholinergic neurons and, to a lesser extent, inhibitory cholinergic neurons. In the antrum, bombesin/GRP acts indirectly on somatostatin cells by stimulating release of gastrin and, to a lesser extent, by activating inhibitory cholinergic neurons. A dual paracrine pathway links gastrin and somatostatin secretion in the antrum.