Stimulation of α-adrenoceptors inhibits cholesterol synthesis in freshly isolated human mononuclear leukocytes

Abstract

Specific agonists and antagonists for α 1- and α 2-adrenoceptors were used to determine an α-adrenoceptor-mediated action of adrenaline on the rate of sterol synthesis from [ 14C]acetate in freshly isolated human mononuclear leukocytes. In the presence of the β-adrenergic blocker propranolol (1μM), adrenaline (100μM) and noradrenaline (100μM) suppressed sterol synthesis by 36% and 38%, respectively, suggesting an action via α-adrenoceptors. The catecholamine effect could be mimicked by α 2-selective β-phenethylamines including α-methylnoradrenaline, but not by imidazolines. α 1-Selective agonists like phenylephrine and methoxamine had no effect on the pathway. Accordingly, the effects of adrenaline and the α 2-selective agonist α-methylnoradrenaline on sterol synthesis were attenuated by the unselective α-antagonist phentolamine and the selective α 2-antagonist yohimbine, but not by the α 1-antagonist prazosin. The results provide evidence that catecholamines can affect sterol synthesis in human mononuclear leukocytes by stimulating α-adrenoceptors of the α 2-subtype.