Systemic urocortin 2, but not urocortin 1 or stressin 1-A, suppresses feeding via CRF2 receptors without malaise and stress.
Br J Pharmacol
; 164(8): 1959-75, 2011 Dec.
Article
en En
| MEDLINE
| ID: mdl-21627635
ABSTRACT
BACKGROUND AND PURPOSE:
Infusion of corticotropin-releasing factor (CRF)/urocortin (Ucn) family peptides suppresses feeding in mice. We examined whether rats show peripheral CRF/Ucn-induced anorexia and determined its behavioural and pharmacological bases. EXPERIMENTALAPPROACH:
Male Wistar rats (n= 5-12 per group) were administered (i.p.) CRF receptor agonists with different subtype affinities. Food intake, formation of conditioned taste aversion and corticosterone levels were assessed. In addition, Ucn 1- and Ucn 2-induced anorexia was studied in fasted CRF(2) knockout (n= 11) and wild-type (n= 13) mice. KEYRESULTS:
Ucn 1, non-selective CRF receptor agonist, reduced food intake most potently (~0.32 nmol·kg(-1) ) and efficaciously (up to 70% reduction) in fasted and fed rats. The peptides' rank-order of anorexic potency was Ucn 1 ≥ Ucn 2 > >stressin(1) -A > Ucn 3, and efficacy, Ucn 1 > stressin(1) -A > Ucn 2 = Ucn 3. Ucn 1 reduced meal frequency and size, facilitated feeding bout termination and slowed eating rate. Stressin(1) -A (CRF(1) agonist) reduced meal size; Ucn 2 (CRF(2) agonist) reduced meal frequency. Stressin(1) -A and Ucn 1, but not Ucn 2, produced a conditioned taste aversion, reduced feeding efficiency and weight regain and elicited diarrhoea. Ucn 1, but not Ucn 2, also increased corticosterone levels. Ucn 1 and Ucn 2 reduced feeding in wild-type, but not CRF(2) knockout, mice. CONCLUSIONS AND IMPLICATIONS CRF(1) agonists, Ucn 1 and stressin(1) -A, reduced feeding and induced interoceptive stress, whereas Ucn 2 potently suppressed feeding via a CRF(2) -dependent mechanism without eliciting malaise. Consistent with their pharmacological differences, peripheral urocortins have diverse effects on appetite.
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Péptidos Cíclicos
/
Estrés Fisiológico
/
Hormona Liberadora de Corticotropina
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Receptores de Hormona Liberadora de Corticotropina
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Urocortinas
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Conducta Alimentaria
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
Br J Pharmacol
Año:
2011
Tipo del documento:
Article