In vivo IL-1β-induced modulation of G-protein α O subunit subclass in the hypothalamic ventromedial nucleus: implications to IL-1β-associated anorexia

Abstract

The intracerebroventricular (i.c.v.) administration of interleukin-1β (IL-1β) induces anorexia in rats at doses that yield estimated pathophysiological concentrations in the cerebrospinal fluid. IL-1β also induces anorexia when administered into the hypothalamic ventromedial nucleus (VMN), an important brain site for the control of feeding. A variety of guanine nucleotide binding protein (G-protein) coupled receptors (e.g., for neurotransmitters and neuropeptides) participate in the integrative regulation of feeding. Our previous studies reported that the VMN G-protein α O common subunit subclass is involved in the control of normal feeding, and that IL-1β modulates calcium channel currents via a pertussis toxin (PTX)-sensitive G-protein (Gα O/Gα i). Here, we examined the profile of Gα O protein expression in the hypothalamic VMN during IL-1β-induced anorexia. Intracerebroventricular microinfusion of IL-1β (0.5 to 8.0 ng/24 h for 72 h) into the third cerebral ventricle dose-dependently induced anorexia ( p<0.001) and decreased the VMN Gα O common protein levels ( p<0.001). Heat-inactivated IL-1β and IL-1β plus IL-1 receptor antagonist (a competitive inhibitor of IL-1β action) had no effect on food intake or on VMN Gα O common protein content. RT-PCR analysis of VMN RNA from IL-1β-treated rats generated an expression profile for Gα O common subunit; however, no modulation at the mRNA level was observed. The results suggest that anorexia induced by the central administration of IL-1β involves modification of G-protein α O common subunit profile in the central nervous system.