Inhibition of acid formation and stimulation of somatostatin release by cholecystokinin-related peptides in rabbit gastric glands.
1. The purpose of the present study was to investigate the role of somatostatin in the inhibition of acid production induced by caerulein and cholecystokinin (CCK) in isolated rabbit gastric glands. Acid production was estimated by the aminopyrine technique. 2. Exogenous somatostatin 14 and somatostatin 28 (10(-7) M) reduced to a similar extent the aminopyrine uptake produced by 5 x 10(-5) M-histamine during the course of 40 min incubation. 3. Significant inhibition of histamine-stimulated aminopyrine accumulation occurred at a somatostatin 14 concentration of 10(-9) M. 4. Caerulein and CCK octapeptide (10(-13)-10(-7) M) were found to release somatostatin from isolated gastric glands in a dose-dependent manner. The dose-response relationships for somatostatin release and inhibition of aminopyrine uptake were similar. Thus, the half-maximal dose approximations for somatostatin release and inhibition of aminopyrine uptake were 0.5 and 1.4 x 10(-9) M respectively for CCK octapeptide and 0.9 and 2.5 x 10(-11) M for caerulein. Heptadecapeptide gastrin proved to be a very poor releaser of somatostatin in the system used. The CCK octapeptide-induced somatostatin release was time dependent and the concentrations of somatostatin that accumulated in the incubation medium were similar to those of exogenous somatostatin that were needed to evoke inhibition. 5. The present results support the concept that cholecystokinin inhibits gastric acid secretion by releasing somatostatin from endocrine-like cells in the gastric mucosa. It is suggested that cholecystokinin-related peptides may play a physiological role in inhibiting gastric acid secretion. A similar role for gastrin is not supported by the present study.
Bengtsson
P
P
Department of Physiology, Faculty of Veterinary Medicine, Swedish University of Agricultural Sciences, Uppsala, Sweden.
Lundqvist
G
G
Nilsson
G
G
D000818:Animals; D002108:Ceruletide / Q000494:pharmacology*; D002766:Cholecystokinin / Q000494:pharmacology*; D005744:Gastric Acid / Q000378:metabolism*; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism*; D006632:Histamine / Q000494:pharmacology*; D066298:In Vitro Techniques; D011817:Rabbits; D012844:Sincalide / Q000494:pharmacology*; D013004:Somatostatin / Q000378:metabolism* / Q000494:pharmacology; D053561:Somatostatin-28
D013004:Somatostatin; D053561:Somatostatin-28; D006632:Histamine; D002108:Ceruletide; D002766:Cholecystokinin; D012844:Sincalide