Cholecystokinin type A and type B receptor antagonists produce opposing effects on cholecystokinin-stimulated beta-endorphin secretion from the rat pituitary.
Cholecystokinin octapeptide (CCK-8) is a potent corticotroph secretagogue. Consistent with earlier reports, the present results demonstrate that CCK-8 administration to rats elevates circulating beta-endorphin and adrenocorticotropin, but not alpha-melanocyte-stimulating hormone concentrations. This response was blocked by dexamethasone pretreatment, but not by vagotomy, and it could not be reproduced by i.c.v. CCK-8 injection, evidence that CCK-8 exerts its effects by directly activating cholecystokinin (CCK) receptors localized on anterior pituitary corticotrophs rather than in brain or the vagus nerve. Subsequent experiments demonstrated further that type A CCK receptors primarily mediate the stimulatory effect of CCK-8 on corticotroph secretion. Thus, devazepide, a selective CCK-A receptor antagonist, produced a dose-related inhibition of the CCK-8-stimulated rise in circulating beta-endorphin concentrations. Less selective CCK-A antagonists, including proglumide and lorglumide, produced little or no effect, however. Unexpectedly, the CCK-B receptor antagonist, L-365,260, enhanced the response to CCK-8, an effect diametrically opposite to that produced by CCK-A antagonists. These observations indicate that CCK-A and CCK-B receptors mediate quite different, if not opposing, roles in regulating corticotroph secretion.
Millington
W R
WR
Division of Molecular Biology and Biochemistry, University of Missouri-Kansas City.
Mueller
G P
GP
Lavigne
G J
GJ
D000818:Animals; D001570:Benzodiazepinones / Q000494:pharmacology; D002766:Cholecystokinin / Q000037:antagonists & inhibitors; D020109:Devazepide; D004305:Dose-Response Relationship, Drug; D007274:Injections, Intraperitoneal; D007276:Injections, Intraventricular; D008297:Male; D010902:Pituitary Gland / Q000187:drug effects* / Q000378:metabolism; D011863:Radioimmunoassay; D051381:Rats; D011919:Rats, Inbred Strains; D011949:Receptors, Cholecystokinin / Q000187:drug effects* / Q000378:metabolism; D012844:Sincalide / Q000008:administration & dosage / Q000494:pharmacology*; D013758:Tetragastrin / Q000008:administration & dosage / Q000494:pharmacology*; D014628:Vagotomy; D001615:beta-Endorphin / Q000097:blood / Q000378:metabolism*
D001570:Benzodiazepinones; D011949:Receptors, Cholecystokinin; D013758:Tetragastrin; D001615:beta-Endorphin; D002766:Cholecystokinin; D020109:Devazepide; D012844:Sincalide