TY - JOUR T1 - STUDIES ON IRREVERSIBLE BINDING OF RADIOACTIVITY FROM [<sup>14</sup>C]HALOTHANE TO RAT HEPATIC MICROSOMAL LIPIDS AND PROTEIN JF - Drug Metabolism and Disposition JO - Drug Metab Dispos SP - 469 LP - 476 VL - 2 IS - 5 AU - RUSSELL A. VAN DYKE AU - A. JAY GANDOLFI Y1 - 1974/09/01 UR - http://dmd.aspetjournals.org/content/2/5/469.abstract N2 - Radioactivity from 14C-labeled halothane has been shown to bind irreversibly to hepatic cellular constituents, with the greatest amount bound to microsomes. Microsomes from isolated livers that had been perfused for 2 hours with [14C]halothane were solubilized with sodium deoxycholate and sonication, and the resulting solution was chromatographed on DEAE-cellulose, Bio-Gel P-30, and DEAE-Sephadex. The radioactivity was not associated with any known microsomal enzymatic activity or with any protein peak. However, the radioactivity was associated with those fractions containing lipid phosphate. This radioactivity was extractable with chloroform-methanol, and thin-layer chromatography of this extract indicated that it was bound to phospholipids, with the largest amount bound to phosphatidylethanolamine and lecithin. Experiments with [36Cl]halothane yielded similar results. In vivo experiments revealed that, at 12 hours after administration of [14C]halothane, the radioactivity was bound to protein and not to phospholipids. Copyright © 1974 by The American Society for Pharmacology and Experimental Therapeutics ER -