Effect of chronic ethanol treatment of Ca2+-inhibited adenylyl cyclase in mouse striatum.
In the present study, to investigate the possibility that chronic ethanol treatment might alter Ca2+-inhibited type 5 adenylyl cyclase (AC) activity, we examined the effect of chronic ethanol treatment on striatal dopaminergic signal transduction, especially the AC system, in mice. We fed male C57BL/6 mice for 7 days with a 5% ethanol-containing or control liquid diet. Basal and forskolin-stimulated AC activities were reduced in striatal membranes of ethanol-treated mice. 5'-guanylylimidodiphosphate-stimulated AC activity was also decreased in ethanol-treated mice. But no significant differences were observed in the levels of the guanine nucleotide binding protein subunits Gs alpha and Gi1alpha&2alpha, determined by immunoblotting, between ethanol-treated and control mice. These results indicated that the function of the catalytic subunit of AC was decreased in the straitum of chronically ethanol-treated mice. We further examined the inhibitory regulation of AC activity in the context of a change of type 5 AC. Inhibition of forskolin-stimulated AC activity by 10 microM free Ca2+ was smaller in ethanol-treated mice than in control mice. However, the protein level of type 5 AC in the striatum, determined by immunoblotting, was not significantly different between ethanol-treated and control mice. These findings suggest that Ca2+-inhibited, presumably type 5, AC activity is reduced in mouse striatum by chronic ethanol treatment, and that this reduction is not due to a decrease in type 5 AC expression.
Ikeda
H
H
Department of Neuropsychiatry, School of Medicine, Sapporo Medical University, Japan.
Hatta
S
S
Ozawa
H
H
Ohshika
H
H
Saito
T
T
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000067956:Adenylyl Cyclase Inhibitors; D000437:Alcoholism / Q000201:enzymology*; D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D003342:Corpus Striatum / Q000201:enzymology*; D000242:Cyclic AMP / Q000494:pharmacology; D004298:Dopamine / Q000502:physiology; D018491:Dopamine Agonists / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D000431:Ethanol / Q000008:administration & dosage / Q000494:pharmacology*; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology; D015151:Immunoblotting; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015398:Signal Transduction
D000067956:Adenylyl Cyclase Inhibitors; D018491:Dopamine Agonists; D004791:Enzyme Inhibitors; D006165:Guanylyl Imidodiphosphate; D000431:Ethanol; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D000242:Cyclic AMP; D002118:Calcium; D004298:Dopamine