Genetic up-regulation of calcium channels in a cellular model of ethanol dependence.
Bovine adrenal chromaffin cells were maintained in culture medium containing ethanol (200 mM) for 6 days. Cultures maintained in ethanol were viable and were morphologically similar to controls. There was a greater than 100% increase in the number of [3H]dihydropyridine calcium channel antagonist binding sites on the cell membranes from ethanol-treated cultures, which could be prevented by concomitant exposure to cycloheximide (5 micrograms.ml-1) and the mRNA synthesis inhibitor, anisomycin (10 micrograms.ml-1) implicating de novo synthesis of protein and genetic regulation, respectively. Release of catecholamines, induced by 18 mM K+, from cultures grown in ethanol was enhanced. The increased release of catecholamines was inhibited by nM concentrations of dihydropyridine calcium channel antagonists, implying that an increase in the number of dihydropyridine-sensitive calcium channels accounts for this functional alteration.
Harper
J C
JC
Department of Pharmacology, King's College, Strand, London, U.K.
Brennan
C H
CH
Littleton
J M
JM
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000313:Adrenal Medulla / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D000437:Alcoholism / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D015220:Calcium Channels / Q000502:physiology*; D002395:Catecholamines / Q000378:metabolism; D002417:Cattle; D002478:Cells, Cultured; D008954:Models, Biological; D009568:Nitrendipine / Q000494:pharmacology; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics; D011978:Receptors, Nicotinic / Q000378:metabolism; D015854:Up-Regulation / Q000235:genetics*
D015220:Calcium Channels; D002395:Catecholamines; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D011978:Receptors, Nicotinic; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D009568:Nitrendipine