Endocrinology, Vol 129, 1312-1316, Copyright © 1991 by Endocrine Society

ARTICLES

Differential antagonist activity of alpha-helical corticotropin- releasing factor9-41 in three bioassay systems

L Fisher, C Rivier, J Rivier and M Brown
Department of Pharmacology, College of Medicine, University of Arizona Health Sciences Center, Tucson 85724.

Studies were performed in conscious unrestrained rats to compare the ability of the CRF receptor antagonist, alpha-helical CRF9-41, to inhibit the actions of CRF in three in vivo bioassay systems. When both peptides were administered intracerebroventricularly, an antagonist:agonist ratio between 6:1-12:1 was required to abolish CRF- induced elevations of plasma catecholamine levels. When both peptides were administered iv, CRF-induced hypotension and tachycardia were completely prevented by an antagonist:agonist ratio of 6:1, whereas total blockade of CRF-induced elevations of plasma ACTH and beta- endorphin levels required an antagonist:agonist ratio of 3000:1. These results demonstrate marked differences in the ability of alpha-helical CRF9-41 to antagonize various biological actions of CRF and support the existence of multiple CRF receptor subtypes.

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