Olubadewo J O, Heimberg M
Department of Pharmacology, University of Tennessee, Memphis 38163.
Biochem Pharmacol. 1993 Jun 22;45(12):2441-7. doi: 10.1016/0006-2952(93)90225-l.
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.
采用[1-14C]油酸，在新鲜分离的大鼠肝细胞中研究了抗高血压肾上腺素能受体拮抗剂（普萘洛尔、酚妥拉明和美托洛尔）改变肝脏脂质代谢的可能性。普萘洛尔（1.8×10-4M）和酚妥拉明（1.4×10-4M）分别使[1-14C]油酸掺入胆固醇酯的量增加51%和92%，使生酮作用分别降低46%和62%。虽然两种药物均不影响[1-14C]油酸掺入总磷脂，但普萘洛尔使甘油三酯合成降低37%。普萘洛尔和酚妥拉明的这些作用可能不是通过β或α受体抑制产生的，因为肾上腺素和去甲肾上腺素均不能逆转肾上腺素能受体拮抗剂的作用。虽然肾上腺素和去甲肾上腺素本身不会改变[1-14C]油酸掺入甘油三酯、磷脂、胆固醇酯或酮体，但它们会刺激14CO2的产生（对照组5.6±1.3；肾上腺素7.6±1.1；去甲肾上腺素9.1±0.2nmol油酸掺入/mg蛋白质），酚妥拉明和普萘洛尔可逆转这些作用。数据表明，肾上腺素能受体拮抗剂对油酸的肝脏代谢有直接作用。
