L-tyrosine and nicotine induce synthesis of l-Dopa and norepinephrine in human lymphocytes

Abstract

Catecholamines (CA) were studied in peripheral human lymphocytes in basal conditions as well as after l-tyrosine and/or acetylcholine (ACh) stimulation. Nicotinic and muscarinic receptor activation and blockade were assessed. CA were determined after ultrasonic cell disruption in peripheral lymphocytes after incubation (1 h at 37°C) with the chemicals employed. l-tyrosine significantly increased ( P<0.01) l-Dopa and norepinephrine (NE) content of lymphocytes. ACh in the low μM range did not modify, whereas ACh (60 μM) and (120 μM) significantly increased ( P<0.01), both l-Dopa and NE intracellular levels. l-tyrosine plus ACh (60 μM) or (120 μM) significantly increased ( P<0.01) intracellular l-Dopa and NE versus control, versus l-tyrosine alone and versus ACh alone. The increase was higher than the algebraic sum of the individual increases. Nicotine (250 μM), but not muscarine (50 μM), significantly increased l-Dopa and NE in lymphocytes. Tetraethylammonium (500 μM) (nicotinic blocker), but not atropine (100 μM) (muscarinic blocker), inhibited the ACh-mediated increase of intracellular l-Dopa and NE. These data show that lymphocyte synthesis of CA is under nicotinic control. Since intracellular l-Dopa after l-tyrosine plus ACh increased 6-fold versus basal, 2-fold versus l-tyrosine alone and 3-fold versus ACh alone, it is concluded that ACh might regulate CA synthesis in lymphocytes through an activation of the rate limiting enzyme tyrosine hydroxylase.