Abstract
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.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adrenocorticotropic Hormone / blood*
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Animals
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Biological Assay
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Blood Pressure / drug effects*
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Cerebral Ventricles / drug effects
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Cerebral Ventricles / physiology*
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Corticotropin-Releasing Hormone / administration & dosage
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Corticotropin-Releasing Hormone / antagonists & inhibitors
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Corticotropin-Releasing Hormone / pharmacology*
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Dose-Response Relationship, Drug
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Epinephrine / blood*
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Heart Rate / drug effects*
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Injections, Intraventricular
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Male
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Norepinephrine / blood*
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Peptide Fragments / administration & dosage
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Peptide Fragments / pharmacology*
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Protein Conformation
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Rats
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Rats, Inbred Strains
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beta-Endorphin / blood*
Substances
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Peptide Fragments
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beta-Endorphin
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Adrenocorticotropic Hormone
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Corticotropin-Releasing Hormone
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corticotropin releasing hormone (9-41)
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Norepinephrine
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Epinephrine