Somatostatin inhibits pancreatic exocrine secretion via a neural mechanism.
The mechanism of inhibition of pancreatic exocrine secretion by somatostatin is unknown. We hypothesized that somatostatin acts indirectly, via intrinsic pancreatic neurons, to inhibit pancreatic exocrine secretion. To test this hypothesis, amylase and volume outputs in response to secretin (10(-8) mol/L) and cholecystokinin octapeptide (CCK) (10(-8) mol/L) were studied in the rat isolated, perfused, pancreas model. Somatostatin (10(-7) mol/L) significantly inhibited amylase output by 48% compared with control (352 +/- 57 v 676 +/- 85 U/30 min, P less than .05 by ANOVA). Blockade of axonal neuronal transmission by tetrodotoxin (10(-7) mol/L) completely abolished the inhibitory effect of somatostatin (992 +/- 53 U/30 min). Similar effects were seen on volume output. The inhibitory effect of somatostatin on amylase output was not affected by cholinergic receptor blockade with atropine (328 +/- 65 U/30 min) or by sympathetic ganglionic blockade with hexamethonium (360 +/- 68 U/30 min). This suggests that the intrinsic pancreatic neurons responsible for the inhibitory effect of somatostatin are peptidergic. The possibility that somatostatin acts directly on the acinar cell to inhibit exocrine secretion was tested by incubating varying doses of somatostatin (10(-12) to 10(-7) mol/L) with isolated pancreatic acini in the presence of graded concentrations of CCK (10(-12) to 10(-10) mol/L). In this model, CCK alone is a potent stimulant of amylase release, with a Km of 6 X 10(-12) mol/L and a Vmax of 22 +/- 3% total amylase. In this model, somatostatin had no inhibitory effect.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Surgery, University of California San Francisco School of Medicine 94143-0788.
S J
SJ
Mulvihill
N W
NW
Bunnett
Y
Y
Goto
H T
HT
Debas
D000681:Amylases / Q000378:metabolism; D000818:Animals; D002766:Cholecystokinin / Q000494:pharmacology; D008297:Male; D008954:Models, Biological; D009474:Neurons / Q000187:drug effects; D010179:Pancreas / Q000187:drug effects* / Q000294:innervation / Q000378:metabolism; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains; D013004:Somatostatin / Q000494:pharmacology*
D013004:Somatostatin; D002766:Cholecystokinin; D000681:Amylases