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 x 10(-4) M) and phentolamine (1.4 x 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 beta- or alpha-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 14CO2 (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 propranolol. The data suggest that adrenoceptor antagonists exert direct effects on hepatic metabolism of oleate.
Olubadewo
J O
JO
Department of Pharmacology, University of Tennessee, Memphis 38163.
Heimberg
M
M
D000818:Animals; D002250:Carbon Radioisotopes; D002788:Cholesterol Esters / Q000032:analysis; D004837:Epinephrine / Q000494:pharmacology; D007657:Ketone Bodies / Q000032:analysis; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008790:Metoprolol / Q000494:pharmacology*; D009638:Norepinephrine / Q000494:pharmacology; D019301:Oleic Acid; D009829:Oleic Acids / Q000378:metabolism*; D010646:Phentolamine / Q000494:pharmacology*; D010743:Phospholipids / Q000032:analysis; D011433:Propranolol / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011941:Receptors, Adrenergic / Q000187:drug effects*; D014280:Triglycerides / Q000032:analysis
D002250:Carbon Radioisotopes; D002788:Cholesterol Esters; D007657:Ketone Bodies; D009829:Oleic Acids; D010743:Phospholipids; D011941:Receptors, Adrenergic; D014280:Triglycerides; D019301:Oleic Acid; D011433:Propranolol; D008790:Metoprolol; D009638:Norepinephrine; D004837:Epinephrine; D010646:Phentolamine