INHIBITION OF FATTY-ACID SYNTHESIS BY STIMULATION OF ALPHA-ADRENERGIC AND BETA-ADRENERGIC RECEPTORS IN HUMAN MONONUCLEAR LEUKOCYTES

Selective alpha- and beta-adrenergic agonists and antagonists were used to determine the action of catecholamines on fatty acid biosynthesis in freshly isolated human mononuclear leukocytes. Incubation of cells for 22 h in a lipid-free medium resulted in a 4-fold increase in the incorporation of [(14)-C]acetate into fatty acids. Addition of (-)-epinephrine in increasing concentrations to the incubation medium inhibited the rate of fatty acid synthesis by 42 % at a concentration of 0.1 M. Similar effects were observed using (-)-norepinephrine and the beta-agonist isoproterenol. The catecholamine action was diminished by the unselective beta-blocker propranolol and mimicked by dibutyryl cyclic AMP. Since human mononuclear leukocytes possess beta 2-, but not beta 1-adrenoceptors (Brodde, Engel and Hoyer 1981), catecholamines may act via beta-adrenergic receptors of the beta 2-subtype. In addition, it appears that stimulation of alpha-adrenergic receptors inhibits fatty acid synthesis, too. In the presence of a beta-blockade by 1 mu M propranolol, the alpha 2-agonist alpha-methylnorepinephrine, but not the alpha 1-agonist phenylephrine inhibited fatty acid synthesis rate. Accordingly, the epinephrine effect was attenuated by the alpha 2-antagonist yohimbine, but not by the alpha 1-antagonist prazosin. The results provide evidence that catecholamines may inhibit the synthesis rate of fatty acids by stimulation of both, beta 2- and alpha 2-adrenergic receptors.