Mechanisms of adaptation to the effects of ethanol on activation of phospholipase C in NG 108-15 cells.
In this study the effect of different times of exposure to ethanol (1-7 days, 100 mM) on bradykinin and GTP(S)-stimulated activation of phospholipase C in NG 108-15 cells and on the binding of [3H]bradykinin to its receptors was investigated. Ethanol attenuated both agonist and GTP-analogue-induced hydrolysis of phosphoinositides for a period of up to 4 days of treatment, while exerting no effect on binding to bradykinin receptors. However, after 7 days of exposure to ethanol, the agonist-induced activation of phospholipase C was completely resistant to the inhibitory effects of alcohol. This finding correlated to a change in the affinity of the bradykinin receptor population after 7 days of treatment. The results indicate that bradykinin-induced breakdown of phosphatidylinositol 4,5-bisphosphate adapts to the effects of ethanol, after long-term treatment. Possible adaptative changes taking place at the level of the G protein(s), may induce a shift in the affinity of the receptor population and, consequently, serve as a compensatory mechanism to counteract the inhibitory effect of ethanol.
Rodríguez
F D
FD
Department of Psychiatry and Neurochemistry, University of Lund, Sweden.
Simonsson
P
P
Gustavsson
L
L
Alling
C
C
D000222:Adaptation, Physiological / Q000187:drug effects*; D001920:Bradykinin / Q000378:metabolism; D002460:Cell Line; D004789:Enzyme Activation / Q000187:drug effects; D000431:Ethanol / Q000494:pharmacology*; D019204:GTP-Binding Proteins / Q000378:metabolism; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D007295:Inositol Phosphates / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism; D010738:Type C Phospholipases / Q000378:metabolism*
D007295:Inositol Phosphates; D010743:Phospholipids; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D000431:Ethanol; D010738:Type C Phospholipases; D019204:GTP-Binding Proteins; D001920:Bradykinin