Muscarinic receptors, protein kinase c isozymes and proliferation of astroglial cells: Effects of ethanol

Activation of cholinergic muscarinic receptors (primarily the M₃ subtype) causes proliferation of astroglial cells and this effect is inhibited by low concentrations (10-50 mM) of ethanol. Investigations on the signal transduction pathways activated by muscarinic receptors in a human astrocytoma cell line (1321N1) have focused on protein kinases C (PKC). Among PKC isozymes expressed in this cell line (α, ε, ζ), the atypical PKC ζ appears to play a primary role in the mitogenic action of muscarinic agonists. We investigated whether activation of these PKC isozymes may be affected by ethanol at concentrations that can inhibit muscarinic receptor-induced proliferation. Carbachol caused an increase in phorbol ester binding and translocation of PKC ε, however, these were inhibited only by 100-200 mM ethanol. On the other hand, translocation of the atypical PKC ζ to the perinuclear area by carbachol was inhibited by ethanol in a dose-dependent manner (10-100 mM). These results suggest that activation of PKC ζ may represent a relevant target for the inhibitory effect of ethanol on muscarinic receptor-induced glial cell proliferation.