Influence of ethanol on calcium, inositol phospholipids and intracellular signalling mechanisms.
Studies have implicated Ca++ in the actions of ethanol at many biochemical levels. Calcium as a major intracellular messenger in the central nervous system is involved in many processes, including protein phosphorylation enzyme activation and secretion of hormones and neurotransmitters. The control of intracellular calcium, therefore, represents a major step by which neuronal cells regulate their activities. The present review focuses on three primary areas which influence intracellular calcium levels; voltage-dependent Ca++ channels, receptor-mediated inositol phospholipid hydrolysis, and Ca++/Mg++-ATPase, the high affinity membrane Ca++ pump. Current research suggests that a subtype of the voltage-dependent Ca++ channel, the dihydropyridine-sensitive Ca++ channel, is uniquely sensitive to acute and chronic ethanol treatment. Acute exposure inhibits, while chronic ethanol exposure increases 45Ca++-influx and [3H]dihydropyridine receptor binding sites. In addition, acute and chronic exposure to ethanol inhibits, then increases Ca++/Mg++-ATPase activity in neuronal membranes. Changes in Ca++ channel and Ca++/Mg++-ATPase activity following chronic ethanol may occur as an adaptation process to increase Ca++ availability for intracellular processes. Since receptor-dependent inositol phospholipid hydrolysis is enhanced after chronic ethanol treatment, subsequent activation of protein kinase-C may also be involved in the adaptation process and may indicate increased coupling for receptor-dependent changes in Ca++/Mg++-ATPase activity. The increased sensitivity of three Ca++-dependent processes suggest that adaptation to chronic ethanol exposure may involve coupling of one or more of these processes to receptor-mediated events.
Gandhi
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CR
University of Texas Health Science Center, Department of Pharmacology, San Antonio 78284-7764.
Ross
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DH
D000818:Animals; D002118:Calcium / Q000502:physiology*; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D000431:Ethanol / Q000494:pharmacology*; D006801:Humans; D008563:Membrane Lipids / Q000502:physiology; D010716:Phosphatidylinositols / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects*
D015220:Calcium Channels; D008563:Membrane Lipids; D010716:Phosphatidylinositols; D000431:Ethanol; D000252:Calcium-Transporting ATPases; D002118:Calcium