Abstract

1. Human umbilical vein endothelial cells were challenged acutely with adenosine and its analogues to examine whether adenosine modulates L-arginine transport (system y +) and synthesis of nitric oxide (NO) and prostacyclin (PGI 2). 2. L-Arginine transport was stimulated by adenosine (10 ?m, 2 min) and the A 2-receptor agonist 2-p-(2-carboxyethyl)phenethylamino-5'-N-ethylcarboxamidoadenosine (CGS-21680; 100 nM), but not by the A 1-receptor agonist N 6-clopentyladenosine (CPA). 3. Activation of L-arginine transport was inhibited by the A 2-receptor antagonists ZM-241385 and 3,7-dimethyl-1-propargylxanthine (DMPX), but unaffected by the A 1-receptor antagonists 8-cyclopentyl-1,3-dipropylxanthine and 8-phenyltheophylline or the adenosine transport inhibitor nitrobenzylthioinosine. 4. Adenosine and CGS-21680 evoked a rapid membrane hyperpolarization. 5. Adenosine and CGX-21680 induced increases in intracellular cGMP levels, whereas release of PGI 2, was unaffected. N(G)-nitro-L-arginine methyl ester (an NO synthase inhibitor) and the A 2-receptor antagonists ZM-241385 and DMPX prevented increases in cGMP accumulation. 6. Our findings provide the first evidence that activation of human fetal endothelial cell A 2-purinoceptors, but not A 1-purinoceptors, leads to a membrane hyperpolarization and stimulation of basal rates of L-arginine transport and NO biosynthesis.