RT Journal Article
SR Electronic
T1 Role of Corticotropin-Releasing Factor (CRF) Receptors in the Anorexic Syndrome Induced by CRF
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 799
OP 806
VO 293
IS 3
A1 Pelleymounter, Mary Ann
A1 Joppa, Margaret
A1 Carmouche, Michelle
A1 Cullen, Mary Jane
A1 Brown, Brock
A1 Murphy, Brian
A1 Grigoriadis, Dimitri E.
A1 Ling, Nick
A1 Foster, Alan C.
YR 2000
UL http://jpet.aspetjournals.org/content/293/3/799.abstract
AB 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. The American Society for Pharmacology and Experimental Therapeutics