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

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.

• Authors: M Guizzetti, L G Costa
• Journal: Neurotoxicology (Neurotoxicology) Vol. 21 Issue 6 Pg. 1117-21 (Dec 2000) ISSN: 0161-813X [Print] Netherlands
• PMID: 11233758 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Central Nervous System Depressants
• Isoenzymes
• Muscarinic Agonists
• Receptors, Muscarinic
• Phorbol 12,13-Dibutyrate
• Ethanol
• Carbachol
• Protein Kinase C

Topics

• Astrocytes (drug effects)
• Astrocytoma (enzymology)
• Blotting, Western
• Carbachol (pharmacology)
• Cell Division (drug effects)
• Central Nervous System Depressants (pharmacology)
• Ethanol (pharmacology)
• Humans
• Isoenzymes (metabolism)
• Muscarinic Agonists (pharmacology)
• Phorbol 12,13-Dibutyrate (metabolism)
• Protein Kinase C (metabolism)
• Receptors, Muscarinic (drug effects)
• Subcellular Fractions (drug effects)
• Tumor Cells, Cultured