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

Abstract

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.

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@article{Millington1992CholecystokininTA, title={Cholecystokinin type A and type B receptor antagonists produce opposing effects on cholecystokinin-stimulated beta-endorphin secretion from the rat pituitary.}, author={William R. Millington and Gregory P Mueller and Gilles J. Lavigne}, journal={The Journal of pharmacology and experimental therapeutics}, year={1992}, volume={261 2}, pages={454-61} }