Stimulation of alpha-adrenoceptors inhibits cholesterol synthesis in freshly isolated human mononuclear leukocytes.
Specific agonists and antagonists for alpha 1- and alpha 2-adrenoceptors were used to determine an alpha-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 beta-adrenergic blocker propranolol (1 microM), adrenaline (100 microM) and noradrenaline (100 microM) suppressed sterol synthesis by 36% and 38%, respectively, suggesting an action via alpha-adrenoceptors. The catecholamine effect could be mimicked by alpha 2-selective beta-phenethylamines including alpha-methylnoradrenaline, but not by imidazolines. alpha 1-Selective agonists like phenylephrine and methoxamine had no effect on the pathway. Accordingly, the effects of adrenaline and the alpha 2-selective agonist alpha-methylnoradrenaline on sterol synthesis were attenuated by the unselective alpha-antagonist phentolamine and the selective alpha 2-antagonist yohimbine, but not by the alpha 1-antagonist prazosin. The results provide evidence that catecholamines can affect sterol synthesis in human mononuclear leukocytes by stimulating alpha-adrenoceptors of the alpha 2-subtype.
Müller-Wieland
D
D
Klinik II und Poliklinik für Innere Medizin, Universität zu Köln Cologne, Germany.
Krone
W
W
D002784:Cholesterol / Q000096:biosynthesis*; D003000:Clonidine / Q000494:pharmacology; D004298:Dopamine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004837:Epinephrine / Q000494:pharmacology; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D009638:Norepinephrine / Q000494:pharmacology; D010646:Phentolamine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects* / Q000502:physiology*; D013261:Sterols / Q000378:metabolism
D011942:Receptors, Adrenergic, alpha; D013261:Sterols; D002784:Cholesterol; D011433:Propranolol; D003000:Clonidine; D004298:Dopamine; D009638:Norepinephrine; D004837:Epinephrine; D010646:Phentolamine