Effects of Chronic Ethanol Exposure on Cardiac Receptor‐Adenylyl Cyclase Coupling: Studies in Cultured Embryonic Chick Myocytes and Ethanol Fed Rats

Abstract

Ethanol effects in the brain appear to be mediated at least in part by an alteration in receptor-effector coupling via guanine nucleotide-binding regulatory proteins (G proteins). To test the hypothesis that a similar pathway participates in the cardiotoxic effects of ethanol, we assessed the effects of chronic ethanol on two commonly used experimental models: embryonic chick myocytes in culture and ventricular myocardium from chronically fed rats. Ethanol had no effect on either the function or quantity of G proteins as assessed by effector-stimulated adenylyl cyclase activity and the levels of ADP-ribosylation substrates. In contrast, effector-stimulated adenylyl cyclase activity was significantly altered in the liver of ethanol-fed rats. These results suggest that receptor-effector coupling via G proteins in our two cardiac models is insensitive to ethanol and that ethanol effects may be species or organ specific.

Adenosine A1 receptors mediate chronic ethanol-induced increases in receptor-stimulated cyclic AMP in cultured hepatocytes

“…Treatment of primary hepatocyte cultures with ethanol over 2-4 days in culture results in increased responsiveness to receptor-stimulated cyclic AMP production (Table 1) [8]. A similar increase in glucagonand forskolin-stimulated cyclic AMP production in liver membranes isolated from rats fed ethanol for 8 weeks has been reported [7]. As adenosine, interacting with adenosine A2 receptors, has been found to mediate the decrease in cyclic AMP production observed in NG108-15 cells after chronic treatment with ethanol [4], we postulated that adenosine may also be involved in the effects of ethanol on cyclic AMP production in cultured hepatocytes.…”

“…This desensitization has been observed after ethanol exposure of cultured NG108-15 neuroblastoma x glioma and S49 lymphoma cells [2,4], as well as in rat cortex after long-term ethanol consumption [3] and peripheral lymphocytes from chronic alcoholics [5,6]. In contrast, increased receptor-and forskolin-stimulated cyclic AMP production has been reported in rat liver membranes after chronic alcohol consumption [7]. Similarly, chronic exposure of primary cultures of rat hepatocytes to ethanol increases receptor-and forskolin-stimulated cyclic AMP levels [8].…”

G-protein regulation of adenylate cyclase activity in rat prostatic membranes after chronic ethanol ingestion

“…In fact, when we studied the behavior of another receptor-mediated event in the present experimental model, we observed that ␤-adrenoceptor stimulation of adenylate cyclase activity increased in prostate after chronic ethanol intake. Similar protocols of ethanol feeding also resulted in disparities among tissues, for example, an increase in ␤-agonist-stimulated adenylate cyclase activity in rat myocardium [31] or in the cerebellar tissues, but not in hippocampus from ethanol-fed mice [32].…”

Effects of the lifestyle habits in breast cancer transcriptional regulation

“…On the other hand, the investigation of the effects of ethanol upstream of the CP450Arom transcription found that acute and chronic exposure to ethanol concentrations above 0.5 % provides a greater stability to adenylyl cyclase (AC), blocks the Gαi function and promotes an irregular increase in cAMP production [ 54 , 57 – 59 ]. This increase in cAMP levels in turn promotes the transactivation of target genes for CREB, such as CP450Arom [ 53 ] and the mitogen agonist belonging to the endothelial growth factor family, Amphiregulin (Amph) [ 48 , 60 , 61 ].…”