Lack of involvement of protein kinase C in ethanol-induced inhibition of metabotropic-glutamate receptor function in primary cultures of astrocytes.
The stimulation of [3H] inositol phosphate (InP) formation by the selective metabotropic-glutamate receptor agonist, 1S, 3R-ACPD, was significantly reduced in rat cortical astrocytes chronically exposed to 100 mM ethanol for 4 days. Under the same conditions, chronic ethanol either increased or did not affect the InP responses to norepinephrine and carbachol, respectively. The InP responses to all three agonists were sensitive to phorbol 12-myristate 13-acetate. Although the protein kinase C inhibitors, calphostin C and staurosporine, significantly relieved the ethanol induced inhibtion of the InP response to 1S, 3R-ACPD, these responses were still significantly less than corresponding values obtained from control cells treated with these inhibitors. The data suggests that mechanisms in addition to protein kinase C are responsible for the ethanol induced inhibition of metabotropic-glutamate function.
Smith
T L
TL
Department of Veterans Affairs Medical Center, Tucson, AZ 85723, USA.
Bitrick
M S
MS
D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism; D002478:Cells, Cultured; D004789:Enzyme Activation; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D009281:Naphthalenes; D011083:Polycyclic Compounds / Q000494:pharmacology; D011247:Pregnancy; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors* / Q000502:physiology; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000470:Alkaloids; D009281:Naphthalenes; D011083:Polycyclic Compounds; D018094:Receptors, Metabotropic Glutamate; D000431:Ethanol; D011493:Protein Kinase C; D019311:Staurosporine; C058819:calphostin C; D013755:Tetradecanoylphorbol Acetate