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 (alpha, epsilon, zeta), the atypical PKCzeta 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 PKCepsilon, however, these were inhibited only by 100-200 mM ethanol. On the other hand, translocation of the atypical PKCzeta to the perinuclear area by carbachol was inhibited by ethanol in a dose-dependent manner (10-100 mM). These results suggest that activation of PKCzeta may represent a relevant target for the inhibitory effect of ethanol on muscarinic receptor-induced glial cell proliferation.
Department of Environmental Health, University of Washington, Seattle 98105-6099, USA.
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Guizzetti
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Costa
D001253:Astrocytes / Q000187:drug effects*; D001254:Astrocytoma / Q000201:enzymology; D015153:Blotting, Western; D002217:Carbachol / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D000431:Ethanol / Q000494:pharmacology*; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D018721:Muscarinic Agonists / Q000494:pharmacology; D015240:Phorbol 12,13-Dibutyrate / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism*; D011976:Receptors, Muscarinic / Q000187:drug effects*; D013347:Subcellular Fractions / Q000187:drug effects; D014407:Tumor Cells, Cultured
D002492:Central Nervous System Depressants; D007527:Isoenzymes; D018721:Muscarinic Agonists; D011976:Receptors, Muscarinic; D015240:Phorbol 12,13-Dibutyrate; D000431:Ethanol; D002217:Carbachol; D011493:Protein Kinase C