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Vol. 293, Issue 3, 799-806, June 2000

Role of Corticotropin-Releasing Factor (CRF) Receptors in the Anorexic Syndrome Induced by CRF1

Mary Ann Pelleymounter, Margaret Joppa, Michelle Carmouche, Mary Jane Cullen, Brock Brown, Brian Murphy, Dimitri E. Grigoriadis, Nick Ling and Alan C. Foster

Departments of Neuroscience, Pharmacology, and Peptide Chemistry, Neurocrine Biosciences, San Diego, California

Genetic manipulations of corticotropin-releasing factor (CRF)1 and CRF2 receptors have resulted in data suggesting that the CRF2 receptor could mediate the effects of CRF on appetite or satiety. We have attempted to obtain pharmacological evidence for this hypothesis by comparing the ability of a high-affinity peptide, mixed CRF antagonist [cyclo 30-33,f12,L18,21E30, A32,K33]sucker fish urotensin (12-41)NH2 [cUTSN (12-41)] with a small-molecule CRF1-selective antagonist, NBI-27914, and a CRF2-selective peptide antagonist, antisauvagine-30, to attenuate the anorexic effects of CRF. We also monitored other behaviors that accompanied CRF-induced anorexia. CRF-induced anorexia was significantly correlated with a reduction in locomotor activity and an increase in freezing behavior and piloerection. cUTSN (12-41) and antisauvagine-30 significantly attenuated the effects of CRF (0.04 nmol) on food intake along with the behavioral syndrome that accompanied anorexia. In contrast, NBI-27914 did not attenuate either of the above-mentioned CRF-induced phenomena when given centrally at doses ranging from 0.13 to 10 nmol/2.5 µl or when given orally at 20 to 40 mg/kg. Although these data support the hypothesis that the CRF2 receptor mediates the appetite suppression induced by CRF, they also suggest that the CRF2 receptor could mediate the stress-like behaviors that accompany CRF-induced appetite suppression.

1 This study was supported in part by Grant 1R44NS35410-02 funded through the Small Business Innovative Research program at the National Institutes of Health.

0022-3565/00/2933-0799$03.00/0
THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
Copyright © 2000 by The American Society for Pharmacology and Experimental Therapeutics


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