Effects of ethanol on neurotransmitter release and intracellular free calcium in PC12 cells.
The effect of ethanol on muscarine-stimulated release of l-[3H]norepinephrine ([3H]NE) was studied using the rat pheochromocytoma cell line, PC12. At concentrations of 25 mM and above, ethanol produced a dose-dependent inhibition of muscarine-stimulated release of [3H]NE. The inhibition of muscarine-stimulated transmitter release occurred in the absence of any detectable effect of ethanol on [3H]NE uptake or on muscarinic binding to the cells. However, ethanol produced an inhibition of muscarine-stimulated elevation of intracellular free Ca++ which corresponded with the inhibition of transmitter release. At concentrations greater than 100 mM, ethanol produced an increase in the basal release of [3H]NE. Intracellular free Ca++ also was increased by ethanol concentrations greater than 100 mM. The elevation of basal transmitter release and intracellular free Ca++ by concentrations of ethanol greater than 100 mM occurred independently of the inhibition by ethanol of muscarine-stimulated elevation of intracellular free Ca++ and transmitter secretion. These results suggest that the effects of ethanol on neurotransmitter release are associated with the effects of ethanol on intracellular free Ca++.
Rabe
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Laboratory of Physiological and Pharmacological Studies, National Institute on Alcohol Abuse and Alcoholism, Rockville, Maryland.
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D000310:Adrenal Gland Neoplasms / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000032:analysis*; D000431:Ethanol / Q000494:pharmacology*; D009116:Muscarine / Q000494:pharmacology; D019832:N-Methylscopolamine; D009638:Norepinephrine / Q000378:metabolism*; D010673:Pheochromocytoma / Q000378:metabolism; D051381:Rats; D011976:Receptors, Muscarinic / Q000378:metabolism; D012602:Scopolamine Derivatives / Q000378:metabolism; D014316:Tritium; D014407:Tumor Cells, Cultured
D011976:Receptors, Muscarinic; D012602:Scopolamine Derivatives; D014316:Tritium; D000431:Ethanol; D009116:Muscarine; D002118:Calcium; D019832:N-Methylscopolamine; D009638:Norepinephrine