Inhibition by ethanol and mepacrine of phospholipase-dependent prostaglandin release from the isolated perfused rat lung.
To investigate the possibility that millimolar concentrations of ethanol have a membrane-directed inhibitory effect on phospholipase A2 and prostanoid generation (suggested from previous platelet experiments), we studied the release of prostacyclin, thromboxane A2 and prostaglandin E2 from isolated perfused rat lung. Prostanoid release was evoked by arachidonic acid, bradykinin and ionophore A23187 and was measured after extraction by radioimmunoassay. In these experiments, prostanoid release is dependent upon biosynthesis from fatty acid precursors as there is no endogenous prostanoid storage pool. Arachidonic acid and bradykinin caused enhanced release of more prostacyclin than thromboxane A2 with much less prostaglandin E2 and no detectable prostaglandin F2 alpha, whereas A23187 released equal proportions of prostacyclin and thromboxane A2 with less prostaglandin E2. Ethanol at 50 mM resembled mepacrine (46 microM) in that prostanoid release in response to bradykinin and A23187 was highly significantly reduced with little effect on release induced by arachidonic acid. We suggest that ethanol, like mepacrine, interferes with prostaglandin generation by an action at the phospholipase step. This may be secondary to a physical effect on membrane configuration.
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D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D015232:Dinoprostone; D000431:Ethanol / Q000494:pharmacology*; D066298:In Vitro Techniques; D008168:Lung / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D010740:Phospholipases / Q000037:antagonists & inhibitors*; D010741:Phospholipases A / Q000037:antagonists & inhibitors*; D054467:Phospholipases A2; D011453:Prostaglandins / Q000378:metabolism*; D011458:Prostaglandins E / Q000378:metabolism; D011796:Quinacrine / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013929:Thromboxane B2 / Q000378:metabolism
D011453:Prostaglandins; D011458:Prostaglandins E; D000001:Calcimycin; D000431:Ethanol; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D010740:Phospholipases; D010741:Phospholipases A; D054467:Phospholipases A2; D011796:Quinacrine; D015232:Dinoprostone; D001920:Bradykinin