Effects of adrenergic agonists and antagonists on the metabolism of [1- 14C]oleic acid by rat hepatocytes

The possibility that the antihypertensive adrenoceptor antagonists (propranolol, phentolamine and metoprolol) may alter hepatic lipid metabolism was examined in freshly dispersed rat hepatocytes with [1- 14C]oleate. Propranolol (1.8 × 10 −4 M) and phentolamine (1.4 × 10 −4 M) increased incorporation of [1- −14C]oleate into cholesteryl esters by 51 and 92%, respectively, and decreased ketogenesis by 46 and 62%, respectively. While neither drug affected incorporation into total phospholipid, propranolol decreased triglyceride synthesis by 37%. These effects of propranolol and phentolamine may not occur through β- or α-receptor inhibition since neither epinephrine nor norepinephrine reversed the effects of the adrenoceptor antagonists. Although epinephrine and norepinephrine per se did not alter the incorporation of [1- −14C]oleate into triglyceride, phospholipid, cholesteryl esters or ketone bodies, they stimulated the production of 14CO 2 (control 5.6 ± 1.3; epinephrine 7.6 + 1.1; norepinephrine 9.1 ± 0.2 nmol oleate incorporated/mg protein), and these effects were reversed by phentolamine and propanolol. The data suggest that adrenoceptor antagonists exert direct effects on hepatic metabolism of oleate.