title: Cholesterol esterification by rat adrenal gland. Inhibition by local anesthetics in vitro.
abstract: Cholesterol esterification was studied in rat adrenal gland, adrenal homogenates and isolated adrenal microsomes. In whole gland and homogenates, the local anesthetic, lidocaine, inhibited the incorporation of [1-14C]oleate and [1-14C]oleoyl-CoA, respectively, into labeled cholesteryl esters in a dose-dependent manner. Inhibition of sterol esterification in the preparations reached 50% at about 2 mM. Various other local anesthetics (tetracaine, dibucaine and benzocaine) also inhibited sterol esterification in adrenal homogenates but were more potent than lidocaine; in each case, 90% inhibition occurred at anesthetic levels of 1 mM. Since sterol esterification in the adrenal gland is a function of microsomal acyl-CoA: cholesterol acyltransferase (EC 2.3.1.26), the enzyme was assayed in isolated adrenal microsomes in the presence of lidocaine while using [14C]oleoyl-CoA as a substrate for labeled cholesteryl ester formation. Inhibition of the enzymes by lidocaine was confirmed, with 50% inhibition occurring between 0.5 and 0.75 mM lidocaine. Lidocaine may be useful as a tool in studies on the regulation of adrenal sterol esterification.
mesh_terms: D000214:Acyl Coenzyme A / Q000378:metabolism; D000217:Acyltransferases / Q000037:antagonists & inhibitors*; D000311:Adrenal Glands / Q000187:drug effects / Q000201:enzymology*; D000779:Anesthetics, Local / Q000494:pharmacology*; D000818:Animals; D001566:Benzocaine / Q000494:pharmacology; D002788:Cholesterol Esters / Q000378:metabolism*; D003992:Dibucaine / Q000494:pharmacology; D008012:Lidocaine / Q000494:pharmacology; D008297:Male; D009829:Oleic Acids / Q000378:metabolism; D051381:Rats; D002785:Sterol O-Acyltransferase / Q000037:antagonists & inhibitors*; D013748:Tetracaine / Q000494:pharmacology
chemical_list: D000214:Acyl Coenzyme A; D000779:Anesthetics, Local; D002788:Cholesterol Esters; D009829:Oleic Acids; D013748:Tetracaine; C017585:oleoyl-coenzyme A; D008012:Lidocaine; D000217:Acyltransferases; D002785:Sterol O-Acyltransferase; D003992:Dibucaine; D001566:Benzocaine