Comparative effects of chronic exposure to ethanol and calcium channel antagonists on calcium channel antagonist receptors in cultured neural (PC12) cells.
Treatment with 200 mM ethanol for 6 days increased binding of the Ca2+ channel antagonist, (+)-[3H]PN 200-110, to intact PC12 cells in culture. Enhancement of binding by ethanol was due to an increase in binding site number without appreciable change in binding affinity. Long-term exposure to Ca2+ channel antagonist drugs (nifedipine, verapamil, or diltiazem), which, like ethanol, acutely inhibit Ca2+ flux, failed to alter (+)-[3H]PN 200-110 binding to PC12 membranes. Cotreatment of ethanol-containing cultures with the Ca2+ channel agonist, Bay K 8644, did not attenuate the response to ethanol; instead, chronic exposure to Bay K 8644 alone increased (+)-[3H]PN 200-110 binding. These results suggest that chronic exposure to ethanol increases Ca2+ channel antagonist receptor density in living neural cells, but that acute inhibition of Ca2+ flux by ethanol is unlikely to trigger this response.
Marks
S S
SS
Department of Neurology, University of California, San Francisco.
Watson
D L
DL
Carpenter
C L
CL
Messing
R O
RO
Greenberg
D A
DA
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000378:metabolism; D000310:Adrenal Gland Neoplasms / Q000378:metabolism; D000818:Animals; D002120:Calcium Channel Agonists / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels; D000431:Ethanol / Q000494:pharmacology*; D017275:Isradipine; D009417:Nerve Tissue / Q000166:cytology / Q000378:metabolism*; D010069:Oxadiazoles / Q000378:metabolism; D010673:Pheochromocytoma / Q000378:metabolism; D051381:Rats; D011978:Receptors, Nicotinic / Q000378:metabolism*; D013237:Stereoisomerism; D013997:Time Factors; D014407:Tumor Cells, Cultured
D002120:Calcium Channel Agonists; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D010069:Oxadiazoles; D011978:Receptors, Nicotinic; D000431:Ethanol; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D017275:Isradipine