Jo. Olubadewo et M. Heimberg, EFFECTS OF ADRENERGIC AGONISTS AND ANTAGONISTS ON THE METABOLISM OF [1-C-14]OLEIC ACID BY RAT HEPATOCYTES, Biochemical pharmacology, 45(12), 1993, pp. 2441-2447
The possibility that the antihypertensive adrenoceptor antagonists (pr
opranolol, phentolamine and metoprolol) may alter hepatic lipid metabo
lism was examined in freshly dispersed rat hepatocytes with [1-C-14]ol
eate. Propranolol (1.8 x 10(-4) M) and phentolamine (1.4 x 10(-4) M) i
ncreased incorporation of [1-C-14]oleate into cholesteryl esters by 51
and 92%, respectively, and decreased ketogenesis by 46 and 62%, respe
ctively. While neither drug affected incorporation into total phosphol
ipid, propranolol decreased triglyceride synthesis by 37%. These effec
ts of propranolol and phentolamine may not occur through beta- or alph
a-receptor inhibition since neither epinephrine nor norepinephrine rev
ersed the effects of the adrenoceptor antagonists. Although epinephrin
e and norepinephrine per se did not alter the incorporation of [1-C-14
]oleate into triglyceride, phospholipid, cholesteryl esters or ketone
bodies, they stimulated the production of (CO2)-C-14 (control 5.6 +/-
1.3; epinephrine 7.6 +/- 1.1; norepinephrine 9.1 +/- 0.2 nmol oleate i
ncorporated/mg protein), and these effects were reversed by phentolami
ne and propanolol. The data suggest that adrenoceptor antagonists exer
t direct effects on hepatic metabolism of oleate.