L-tyrosine and nicotine induce synthesis of L-Dopa and norepinephrine in human lymphocytes.
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 degrees C) with the chemicals employed. L-tyrosine significantly increased (P < 0.01) L-Dopa and norepinephrine (NE) content of lymphocytes. ACh in the low microM range did not modify, whereas ACh (60 microM) and (120 microM) significantly increased (P < 0.01), both L-Dopa and NE intracellular levels. L-tyrosine plus ACh (60 microM) or (120 microM) 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 microM), but not muscarine (50 microM), significantly increased L-Dopa and NE in lymphocytes. Tetraethylammonium (500 microM) (nicotinic blocker), but not atropine (100 microM) (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.
Musso
N R
NR
Department of Internal Medicine, San Martino Hospital, University of Genoa, Italy. nrmusso@unige.it
Brenci
S
S
Indiveri
F
F
Lotti
G
G
D000109:Acetylcholine / Q000494:pharmacology; D000328:Adult; D001773:Blood Cells / Q000378:metabolism*; D005260:Female; D006801:Humans; D007980:Levodopa / Q000096:biosynthesis*; D008214:Lymphocytes / Q000378:metabolism*; D008297:Male; D009116:Muscarine / Q000494:pharmacology; D009538:Nicotine / Q000494:pharmacology*; D009638:Norepinephrine / Q000096:biosynthesis*; D014443:Tyrosine / Q000494:pharmacology*
D014443:Tyrosine; D007980:Levodopa; D009538:Nicotine; D009116:Muscarine; D000109:Acetylcholine; D009638:Norepinephrine