Differential Antagonist Activity ofα-Helical Corticotropin-Releasing Factor9–41in Three Bioassay Systems*

Abstract
Studies were performed in conscious unrestrained rats to compare the ability of the CRF receptor antagonist, α-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 β-endorphin levels required an antagonist:agonist ratio of 3000:1. These results demonstrate marked differences in the ability of α-helical CRF9–41 to antagonize various biological actions of CRF and support the existence of multiple CRF receptor subtypes. (Endocrinology129: 1312–1316, 1991)

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