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.

Muscarinic receptors, protein kinase C isozymes and proliferation of astroglial cells: effects of ethanol / Guizzetti, M; Costa, L. G.. - In: NEUROTOXICOLOGY. - ISSN 0161-813X. - 21:6(2000), p. 1117-21.

Muscarinic receptors, protein kinase C isozymes and proliferation of astroglial cells: effects of ethanol

Costa, L. G.
2000-01-01

Abstract

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.
Muscarinic receptors, protein kinase C isozymes and proliferation of astroglial cells: effects of ethanol / Guizzetti, M; Costa, L. G.. - In: NEUROTOXICOLOGY. - ISSN 0161-813X. - 21:6(2000), p. 1117-21.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11381/2837223
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