Regulation of cholecystokinin secretion by food, hormones, and neural pathways in the rat.
Regulation of cholecystokinin (CCK) secretion was studied in conscious unrestrained rats by simultaneous duodenal perfusion with foodstuffs, intravenous infusion of hormones or neural agents, and arterial blood sampling for CCK bioassay. Duodenal infusion of casein resulted in elevation of plasma CCK from fasting level of 0.5 +/- 0.1 to 3.8 +/- 0.4 pM. Casein hydrolysate, calcium, and glucose did not elevate plasma CCK. Infusion of intact fat had a small, but nonsignificant, effect (1.4 +/- 0.4 pM), whereas infusion of oleate increased plasma CCK to 3.7 +/- 0.6 pM. Thus intact protein and fatty acids are the major dietary intestinal stimuli for CCK release in the rat. The CCK response to protein could be inhibited by somatostatin but not by peptide YY (0.2, 2, or 20 micrograms.kg-1.h-1); intravenous infusion of 1 or 10 micrograms.kg-1.h-1 somatostatin decreased casein-stimulated CCK levels to 1.5 +/- 0.2 and 0.9 +/- 0.3 pM, respectively. Stimulation of vagal discharge with 2-deoxy-D-glucose had no effect on basal or protein-stimulated plasma CCK levels; thus CCK release in the rat does not appear to be modulated by central vagal pathways. Gastrin-releasing peptide increased fasting plasma CCK levels to 1.6 +/- 0.1 pM. Administration of the cholinergic agonist bethanechol, while having no effect on fasting CCK level, inhibited protein-stimulated plasma CCK from 3.9 +/- 0.6 to 1.3 +/- 0.3 pM. Cholinergic blockade with atropine, in contrast, had no effect on basal or protein-stimulated plasma CCK. Thus CCK release is stimulated by dietary protein or fatty acid and by gastrin-releasing peptide and inhibited by somatostatin and bethanechol.
Lewis
L D
LD
Department of Physiology, University of California, San Francisco 94143.
Williams
J A
JA
D000818:Animals; D002766:Cholecystokinin / Q000097:blood / Q000378:metabolism*; D003847:Deoxyglucose / Q000494:pharmacology; D004386:Duodenum / Q000378:metabolism*; D004435:Eating; D005215:Fasting; D005502:Food; D005768:Gastrointestinal Hormones / Q000494:pharmacology*; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D019894:Peptide YY; D010455:Peptides / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013004:Somatostatin / Q000494:pharmacology*; D014630:Vagus Nerve / Q000187:drug effects / Q000502:physiology*
D005768:Gastrointestinal Hormones; D010455:Peptides; D019894:Peptide YY; D013004:Somatostatin; D002766:Cholecystokinin; D003847:Deoxyglucose