Cysteamine induces cholecystokinin release from the duodenum. Evidence for somatostatin as an inhibitory paracrine regulator of cholecystokinin secretion in the rat.
To determine whether cholecystokinin secretion is regulated by endogenous somatostatin, somatostatin deficiency was induced in vivo with cysteamine (250 mg/kg body wt, IV) or anti-somatostatin antiserum in anaesthetized rats and in vitro with cysteamine (30 micrograms/mL) in a rat duodenum-incubation system. Cholecystokinin secretion was assessed in vivo by measuring amylase in duodenal perfusates collected at 10-minute intervals for 1 hour and in vitro by a carboxy-terminal radioimmunoassay. Cysteamine induced a marked decrease in duodenal immunoreactive somatostatin both in vivo (50%) and in vitro (60%). The rate of amylase secretion increased from 9.7 +/- 2.1 U (mean +/- SE) to 28.0 +/- 4.8 U at 20 minutes (P less than 0.001). The cholecystokinin-receptor antagonist CR-1392 abolished amylase response for 30 minutes, whereas the more potent antagonists Asperlicin (18.0 mg/kg body wt, IV) and L-364,718 (0.25 mg/kg body wt, IV) caused prolonged blockade. The rate of amylase secretion in gastrectomized animals increased from 7.2 +/- 2.0 U to 15.0 +/- 2.2 U 20 minutes after cysteamine administration (P less than 0.01), indicating that the effect was not due to the presence of gastrin. In vitro, cysteamine caused a nearly fourfold increase in cholecystokinin secretion compared with controls (63.1 +/- 4.9 vs. 15.2 +/- 3.7, respectively; P less than 0.001). In vivo immunoneutralization of circulating somatostatin with a high-affinity and high-capacity antiserum produced no significant change in the rate of amylase secretion. These results suggest that cholecystokinin secretion is tonically inhibited by somatostatin and that this effect is mediated by locally secreted (paracrine) but not by circulating somatostatin.
Abucham
J
J
Department of Medicine, Tufts-New England Medical Center, Boston, Massachusetts.
Reichlin
S
S
D000681:Amylases / Q000378:metabolism; D000818:Animals; D002766:Cholecystokinin / Q000037:antagonists & inhibitors / Q000378:metabolism*; D003543:Cysteamine / Q000494:pharmacology*; D004386:Duodenum / Q000378:metabolism*; D005743:Gastrectomy; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011949:Receptors, Cholecystokinin / Q000187:drug effects; D013004:Somatostatin / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology*
D011949:Receptors, Cholecystokinin; D013004:Somatostatin; D003543:Cysteamine; D002766:Cholecystokinin; D000681:Amylases