Somatostatin inhibits cholecystokinin-induced pancreatic protein secretion via cholinergic pathways.
Although somatostatin is a potent inhibitor of pancreatic exocrine secretion in vivo, its mechanism of action remains unclear. The influence of extrapancreatic nerves and intrapancreatic cholinergic activity on somatostatin-induced inhibition of pancreatic exocrine secretion was studied in conscious dogs. Chronic pancreatic fistulae were created in six mongrel dogs, and a second group of six dogs also underwent complete pancreatic denervation. The pancreatic responses to graded doses of cholecystokinin (12.5-200 ng/kg/h) and bethanechol (57-916 micrograms/kg/h), both alone and during background infusion of somatostatin-14 (800 pm/kg/h), were determined in all dogs. The cholecystokinin dose-response with a somatostatin-14 background was then repeated with the addition of atropine (10 micrograms/kg/h). In both groups of animals, cholecystokinin elicited a dose-dependent increase in pancreatic protein secretion that was inhibited significantly by somatostatin-14. Regardless of the status of extrapancreatic nerves, atropine further inhibited cholecystokinin-induced protein secretion beyond that evoked by somatostatin-14. In both innervated and denervated animals, cholinergic stimulation with bethanechol elicited a dose-dependent increase in pancreatic protein secretion that was unaffected by somatostatin-14. We conclude that extrapancreatic nerves do not mediate the inhibitory effects of somatostatin-14. Somatostatin-14 appears to inhibit cholecystokinin-induced pancreatic secretion by an intrapancreatic cholinergic mechanism.
Brodish
R J
RJ
Department of Surgery, University of Cincinnati School of Medicine, Ohio, USA.
Kuvshinoff
B W
BW
McFadden
D W
DW
Fink
A S
AS
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D018723:Bethanechol / Q000494:pharmacology; D001639:Bicarbonates / Q000378:metabolism; D002766:Cholecystokinin / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D002794:Choline / Q000502:physiology*; D003714:Denervation; D004285:Dogs; D007328:Insulin / Q000494:pharmacology; D010179:Pancreas / Q000187:drug effects / Q000294:innervation / Q000378:metabolism*; D013004:Somatostatin / Q000494:pharmacology*
D001639:Bicarbonates; D007328:Insulin; D018723:Bethanechol; D013004:Somatostatin; D001285:Atropine; D002766:Cholecystokinin; D002794:Choline