Ethanol exposure alters K+- but not bradykinin-induced dopamine release in PC12 cells.
The effects of ethanol on [3H]dopamine release were investigated in cultured PC12 cells using two methods to stimulate dopamine release: exposure to depolarizing concentrations of extracellular K+ and incubation with the highly active secretagogue, bradykinin. Both K+ and bradykinin dose-dependently increased [3H]dopamine release. The mean +/- S.E.M. EC50 for K+ was 35.8 +/- 1.2 mM; for bradykinin it was 1.07 +/- 0.23 x 10(-7) M. The characteristics of the bradykinin-stimulated dopamine release showed it to be dependent on extracellular Ca2+ and was attenuated by 1 mM Co2+ or 1 mM Ni2+. However, release was unaffected by either the voltage-dependent Ca2+ channel antagonist, verapamil, or the dihydropyridine (DHP) Ca2+ channel agonist, BAY K 8644. In contrast, 1 mM Co2+ completely blocked, verapamil inhibited and BAY K 8644 augmented K+-stimulated [3H]dopamine release. PC12 cells acutely exposed to ethanol (100 and 200 mM) showed diminished K+-stimulated [3H]dopamine release but an unaltered bradykinin-stimulated response. Cells exposed to 200 mM ethanol for 6 days showed significantly enhanced [3H]dopamine release in response to high concentrations of K+ but no changes were observed in their response to bradykinin. These data provide evidence that ethanol, within the same cell, can differentially affect neurotransmitter release, dependent upon the secretagogue used.
Oldham
S B
SB
Department of Psychiatry and Biobehavioral Science, University of California, Los Angeles.
Ritchie
T
T
Noble
E P
EP
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000008:administration & dosage / Q000494:pharmacology; D000310:Adrenal Gland Neoplasms / Q000378:metabolism; D000818:Animals; D001920:Bradykinin / Q000008:administration & dosage / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects; D004298:Dopamine / Q000032:analysis / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000008:administration & dosage / Q000494:pharmacology*; D009994:Osmolar Concentration; D010673:Pheochromocytoma / Q000378:metabolism; D011188:Potassium / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D051381:Rats; D013268:Stimulation, Chemical; D014700:Verapamil / Q000008:administration & dosage / Q000494:pharmacology
D015220:Calcium Channels; D000431:Ethanol; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D014700:Verapamil; D011188:Potassium; D001920:Bradykinin; D004298:Dopamine