Effects of alcohol on alpha-adrenergic receptor regulation of calcium ATPase in liver plasma membranes.
The effects of alpha 1- and alpha 2-adrenergic agonists, viz., phenylephrine and clonidine, respectively, were studied on rat liver plasma membrane Ca++-ATPase. Phenylephrine produced a 23% inhibition of enzyme activity at 5 microM. Prazosin, an alpha 1 antagonist, completely prevented the effect of phenylephrine. Clonidine produced a comparable inhibition of Ca++-ATPase, but was not reversed by the antagonist yohimbine, suggesting a lack of functionally significant alpha 2 receptors as previously reported. The results support the role of high-affinity Ca++-ATPase in liver plasma membranes in the control of cytosolic free Ca++ levels through regulation by alpha 1-adrenergic receptors. In vitro and acute ethanol exposure produced inhibition of plasma membrane Ca++-ATPase. In addition, ethanol treatment significantly reversed the inhibitory effect of phenylephrine on Ca++-ATPase. Chronic ethanol exposure for four weeks increased Ca++-ATPase activity over control and increased enzyme activity in the presence of phenylephrine. These results demonstrate that ethanol alters the alpha-adrenergic receptor interaction with Ca++-ATPase resulting in reduced receptor regulation of cytosolic Ca++ levels. These changes may prevent the liver from maintaining Ca++ levels for second messenger functions, such as glycolysis and gluconeogenesis.
D000818:Animals; D000252:Calcium-Transporting ATPases / Q000378:metabolism*; D002462:Cell Membrane / Q000201:enzymology; D003000:Clonidine / Q000494:pharmacology; D004347:Drug Interactions; D000431:Ethanol / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*
D011942:Receptors, Adrenergic, alpha; D010656:Phenylephrine; D000431:Ethanol; D000252:Calcium-Transporting ATPases; D003000:Clonidine