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 less than 0.01) by tetrodotoxin (5 microM) but augmented by atropine (1 microM) (P less than 0.01). In antral segments, both tetrodotoxin and atropine augmented the somatostatin response to bombesin/GRP by 42-45% (P less than 0.01), whereas the gastrin antagonist L 365260 (1 microM) abolished it. The gastrin antagonist augmented the gastrin response to bombesin/GRP by 103% (P less than 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.
Department of Medicine, Medical College of Virginia, Richmond 23249.
M L
ML
Schubert
M J
MJ
Jong
G M
GM
Makhlouf
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001570:Benzodiazepinones / Q000494:pharmacology; D001839:Bombesin / Q000494:pharmacology*; D005748:Gastric Fundus / Q000294:innervation* / Q000378:metabolism; D005755:Gastrins / Q000378:metabolism / Q000502:physiology*; D066298:In Vitro Techniques; D009474:Neurons / Q000502:physiology*; D010671:Phenylurea Compounds; D011706:Pyloric Antrum / Q000378:metabolism*; D051381:Rats; D013004:Somatostatin / Q000378:metabolism*; D013779:Tetrodotoxin / Q000494:pharmacology
D001570:Benzodiazepinones; D005755:Gastrins; D010671:Phenylurea Compounds; C058121:L 365260; D013779:Tetrodotoxin; D013004:Somatostatin; D001285:Atropine; D001839:Bombesin