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.
Division of Molecular Biology, School of Life and Health Sciences, University of Delaware, Newark, DE 19716-2590, USA. crps@udel.edu
C R
CR
Plata-Salamán
C D
CD
Wilson
J M
JM
Ffrench-Mullen
D000818:Animals; D000855:Anorexia / Q000139:chemically induced / Q000503:physiopathology*; D002552:Cerebral Ventricles / Q000187:drug effects / Q000502:physiology*; D017931:DNA Primers; D002149:Energy Intake / Q000187:drug effects; D005247:Feeding Behavior / Q000187:drug effects; D019204:GTP-Binding Proteins / Q000096:biosynthesis / Q000235:genetics*; D007031:Hypothalamus / Q000187:drug effects / Q000502:physiology*; D007263:Infusions, Parenteral; D007375:Interleukin-1 / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D037342:Pertussis Toxin; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014697:Ventromedial Hypothalamic Nucleus / Q000187:drug effects / Q000502:physiology*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D017931:DNA Primers; D007375:Interleukin-1; D012333:RNA, Messenger; D010566:Virulence Factors, Bordetella; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins