title: Brain forskolin binding in mice dependent on and tolerant to ethanol.
abstract: Chronic ethanol ingestion by mice was previously shown to result in decreased activation of adenylate cyclase by guanine nucleotides and beta-adrenergic agonists, and in the loss of the high affinity beta-adrenergic agonist binding site in frontal cortex and hippocampus but not in cerebellum. These results indicate a regional specificity of ethanol's actions on beta-adrenergic receptors, the guanine nucleotide binding protein (Gs) and/or adenylate cyclase. To further detail the anatomical specificity of the effects of ethanol ingestion on receptor-coupled adenylate cyclase (AC) systems we have quantified the binding of [3H]forskolin to brain sections of control and ethanol-fed mice. High-affinity forskolin binding, thought to represent the complex of the alpha-subunit of Gs (as) and AC, was decreased in several brain areas including frontal cortex and hippocampus, but not in cerebellum, nucleus accumbens and certain other brain areas of ethanol-fed mice. Guanine nucleotides, such as Gpp(NH)p, generally enhanced forskolin binding in control animals. In ethanol-fed mice, however, Gpp(NH)p failed to enhance forskolin binding in most brain regions. These findings suggest that chronic ethanol ingestion may decrease the amount or function of as-AC in certain brain regions. Moreover, the regulation of the formation of this complex in different brain regions may affect responses to ethanol ingestion in mice.
authors.affiliation: National Institute on Alcohol Abuse and Alcoholism, Division of Intramural Clinical and Biological Research, Bethesda, MD 20892.
authors.forename: P
authors.initials: P
authors.lastname: Valverius
authors.forename: P L
authors.initials: PL
authors.lastname: Hoffman
authors.forename: B
authors.initials: B
authors.lastname: Tabakoff
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D005576:Colforsin / Q000378:metabolism*; D004361:Drug Tolerance; D000431:Ethanol / Q000008:administration & dosage*; D006160:Guanosine Triphosphate / Q000031:analogs & derivatives*; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D005576:Colforsin; D006165:Guanylyl Imidodiphosphate; D000431:Ethanol; D006160:Guanosine Triphosphate; D000262:Adenylyl Cyclases