Somatostatin inhibits secretin-induced canine pancreatic response via a cholinergic mechanism.
BACKGROUND
Somatostatin inhibits pancreatic exocrine secretion in intact animals but not in vitro, suggesting an indirect effect. The present study examined the influence of extrapancreatic nerves and intrapancreatic cholinergic activity on somatostatin-induced inhibition of pancreatic exocrine secretion in conscious dogs.


METHODS
Seven dogs underwent extrapancreatic denervation and creation of pancreatic fistulae, while a second group of 6 dogs had pancreatic fistulae created without denervation. The pancreatic responses to graded doses of secretin (16-500 ng.kg-1.h-1), both alone and during background infusions of somatostatin-14 (400 and 800 pmol/L.kg-1.hr-1), were determined in all dogs. The secretin dose response was then repeated with a continuous infusion of bethanechol (90 micrograms.kg-1.h-1) both with and without somatostatin-14 (800 pmol/L.kg-1.h-1).


RESULTS
Secretin-induced bicarbonate and protein outputs were significantly inhibited by somatostatin-14 in both the innervated and denervated animals. The inhibitory effects of somatostatin-14 were partially reversed by bethanechol in the innervated animals and completely reversed in the denervated animals. Bethanechol alone potentiated secretin-induced bicarbonate output from both the innervated and denervated pancreas.


CONCLUSIONS
The data suggest that extrapancreatic nerves do not mediate the inhibitory effects of somatostatin-14. Rather, somatostatin-14 appears to inhibit secretin-induced pancreatic response by an intrapancreatic cholinergic mechanism.
Kuvshinoff
B W
BW
Department of Surgery, University of Cincinnati Medical Center, Ohio.
Brodish
R J
RJ
James
L
L
McFadden
D W
DW
Fink
A S
AS
D000818:Animals; D018723:Bethanechol; D001626:Bethanechol Compounds / Q000494:pharmacology; D003714:Denervation; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D010179:Pancreas / Q000187:drug effects* / Q000294:innervation; D010275:Parasympathetic Nervous System / Q000502:physiology*; D012633:Secretin / Q000494:pharmacology*; D013004:Somatostatin / Q000494:pharmacology*
D001626:Bethanechol Compounds; D018723:Bethanechol; D012633:Secretin; D013004:Somatostatin