Cholecystokinin type A and type B receptor antagonists produce opposing effects on cholecystokinin-stimulated beta-endorphin secretion from the rat pituitary

• Published in: The Journal of pharmacology and experimental therapeutics Vol. 261; no. 2; pp. 454 - 461
• Main Authors: MILLINGTON, W. R, MUELLER, G. P, LAVIGNE, G. J
• Format: Journal Article
• Language: English
• Published: Bethesda, MD American Society for Pharmacology and Experimental Therapeutics 01.05.1992
• Subjects: Animals; antagonists; Benzodiazepinones - pharmacology; beta -endorphin; beta-Endorphin - blood; beta-Endorphin - secretion; Biological and medical sciences; Cholecystokinin - antagonists & inhibitors; cholecystokinin A; cholecystokinin B; Devazepide; Dose-Response Relationship, Drug; effects on; Fundamental and applied biological sciences. Psychology; Hormones and neuropeptides. Regulation; Hypothalamus. Hypophysis. Epiphysis. Urophysis; Injections, Intraperitoneal; Injections, Intraventricular; Male; pituitary; Pituitary Gland - drug effects; Pituitary Gland - secretion; Radioimmunoassay; Rats; Rats, Inbred Strains; receptors; Receptors, Cholecystokinin - drug effects; Receptors, Cholecystokinin - metabolism; secretion; Sincalide - administration & dosage; Sincalide - pharmacology; Tetragastrin - administration & dosage; Tetragastrin - pharmacology; Vagotomy; Vertebrates: endocrinology; Endocrine gland; Rat; Rodentia; Peptide hormone; Time response relation; β-Endorphin; Neuropeptide; Site of action; Dose activity relation; Vertebrata; Mammalia; Gastrointestinal hormone; Animal; Pituitary gland; Antagonist; Cholecystokinin; Release; Hormonal receptor
• ISSN: 0022-3565; 1521-0103

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.