Involvement of protein kinase C in ethanol-induced inhibition of NMDA receptor function in cerebellar granule cells.
Ethanol inhibits N-methyl-D-aspartate (NMDA)-stimulated increases in intracellular Ca2+ in cerebellar granule cells apparently by reducing the potency of glycine to act as a co-agonist at the NMDA receptor. The inhibitory effect of ethanol on the NMDA response in these cells can be reversed not only by a high concentration of glycine, but also by the protein kinase inhibitors, staurosporine and calphostin C. We previously showed that activation of protein kinase C in cerebellar granule cells also resulted in inhibition of the NMDA response, and in decreased potency of glycine at the NMDA receptor. Furthermore, the inhibitory effects of ethanol and protein kinase C activation are not additive. These results suggest a role for protein kinase C in ethanol inhibition of NMDA responses in cerebellar granule cells. In contrast, although ethanol can inhibit the response to kainate in these cells in a "competitive" manner, this response is not affected by activation of protein kinase C.
Snell
L D
LD
Department of Pharmacology, University of Colorado Health Sciences Center, Denver 80262.
Tabakoff
B
B
Hoffman
P L
PL
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002531:Cerebellum / Q000187:drug effects* / Q000502:physiology; D046508:Culture Techniques; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000633:toxicity*; D009474:Neurons / Q000187:drug effects; D011493:Protein Kinase C / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors* / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects* / Q000502:physiology
D016194:Receptors, N-Methyl-D-Aspartate; D000431:Ethanol; D011493:Protein Kinase C; D002118:Calcium