Cholesterol esterification by rat adrenal gland. Inhibition by local anesthetics in vitro.

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.