In vivo IL-1beta-induced modulation of G-protein alphaO subunit subclass in the hypothalamic ventromedial nucleus: implications to IL-1beta-associated anorexia.

The intracerebroventricular (i.c.v.) administration of interleukin-1beta (IL-1beta) induces anorexia in rats at doses that yield estimated pathophysiological concentrations in the cerebrospinal fluid. IL-1beta 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 alphaO common subunit subclass is involved in the control of normal feeding, and that IL-1beta modulates calcium channel currents via a pertussis toxin (PTX)-sensitive G-protein (GalphaO/Galphai). Here, we examined the profile of GalphaO protein expression in the hypothalamic VMN during IL-1beta-induced anorexia. Intracerebroventricular microinfusion of IL-1beta (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 GalphaO common protein levels (p<0.001). Heat-inactivated IL-1beta and IL-1beta plus IL-1 receptor antagonist (a competitive inhibitor of IL-1beta action) had no effect on food intake or on VMN GalphaO common protein content. RT-PCR analysis of VMN RNA from IL-1beta-treated rats generated an expression profile for GalphaO common subunit; however, no modulation at the mRNA level was observed. The results suggest that anorexia induced by the central administration of IL-1beta involves modification of G-protein alphaO common subunit profile in the central nervous system.