Role of corticotropin-releasing factor (CRF) receptors in the anorexic syndrome induced by CRF.
Genetic manipulations of corticotropin-releasing factor (CRF)(1) and CRF(2) receptors have resulted in data suggesting that the CRF(2) 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)NH(2) [cUTSN (12-41)] with a small-molecule CRF(1)-selective antagonist, NBI-27914, and a CRF(2)-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 microl or when given orally at 20 to 40 mg/kg. Although these data support the hypothesis that the CRF(2) receptor mediates the appetite suppression induced by CRF, they also suggest that the CRF(2) receptor could mediate the stress-like behaviors that accompany CRF-induced appetite suppression.
Pelleymounter
M A
MA
Department of Neuroscience, Pharmacology, and Peptide Chemistry, Neurocrine Biosciences, San Diego, CA 92121, USA. MPelleymounter@neurocrine.com
Joppa
M
M
Carmouche
M
M
Cullen
M J
MJ
Brown
B
B
Murphy
B
B
Grigoriadis
D E
DE
Ling
N
N
Foster
A C
AC
D000818:Animals; D000855:Anorexia / Q000139:chemically induced*; D001522:Behavior, Animal / Q000187:drug effects; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects; D005260:Female; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D010446:Peptide Fragments / Q000494:pharmacology; D018019:Receptors, Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors / Q000502:physiology*
D010446:Peptide Fragments; D018019:Receptors, Corticotropin-Releasing Hormone; C116607:antisauvagine 30; D003346:Corticotropin-Releasing Hormone