Involvement of adenosine in ethanol-induced changes in G-protein expression in NG108-15 cells?
Previous work has suggested that adenosine may be involved in ethanol-induced heterologous desensitization of adenylate cyclase in NG108-15 cells. It was proposed that chronic ethanol causes adenosine to accumulate extracellularly, activating adenosine A2 receptors and so leading to a reduction in Gs alpha mRNA and Gs alpha protein (Nagy et al., 1989). In this study we further investigated the effect of chronic ethanol on G-protein expression in NG108-15 cells. Pretreatment of NG108-15 cells with ethanol (200 mM, 48h) reduced membrane levels of Gs alpha and Gi alpha but increased Go alpha expression. The effects of ethanol on alpha-subunit expression were not reversed by adenosine deaminase and could not be mimicked by the adenosine agonist 5'- (n-ethyl)-carboxamidoadenosine (NECA). Chronic ethanol pretreatment did not appear to reduce the levels of Gs alpha or Gi alpha 2 mRNA. This same ethanol pretreatment reduced cell proliferation and increased differentiation without altering cell viability. Adenosine deaminase did not reverse any of these effects. These results indicate that ethanol differentially regulates G-protein alpha-subunit expression and induces morphological alterations in these cells independently of extracellular adenosine.
Williams
R J
RJ
Department of Pharmacology, School of Medical Sciences, University of Bristol, U.K.
Veale
M A
MA
Kelly
E
E
D000241:Adenosine / Q000378:metabolism*; D000243:Adenosine Deaminase / Q000494:pharmacology; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D000431:Ethanol / Q000633:toxicity*; D019204:GTP-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006822:Hybrid Cells; D011487:Protein Conformation; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured
D012333:RNA, Messenger; D000431:Ethanol; D000243:Adenosine Deaminase; D019204:GTP-Binding Proteins; D000241:Adenosine