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Activation of A2‐purinoceptors by adenosine stimulates L‐arginine transport (system y+) and nitric oxide synthesis in human fetal endothelial cells.

1997; Wiley; Volume: 499; Issue: 1 Linguagem: Inglês

10.1113/jphysiol.1997.sp021916

1469-7793

Luis Sobrevía, D. L. Yudilevich, G.E. Mann,

Receptor Mechanisms and Signaling

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 (PGI2). 2. L‐Arginine transport was stimulated by adenosine (10 microM, 2 min) and the A2‐receptor agonist 2‐p‐(2‐carboxyethyl)phenethylamino‐5'‐N‐ethylcarboxamidoadenosine (CGS‐21680; 100 nM), but not by the A1‐receptor agonist N6‐cyclopentyladenosine (CPA). 3. Activation of L‐arginine transport was inhibited by the A2‐receptor antagonists ZM‐241385 and 3,7‐dimethyl‐1‐propargylxanthine (DMPX), but unaffected by the A1‐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 CGS‐21680 induced increases in intracellular cGMP levels, whereas release of PGI2 was unaffected. NG‐nitro‐L‐arginine methyl ester (an NO synthase inhibitor) and the A2‐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 A2‐purinoceptors, but not A1‐purinoceptors, leads to a membrane hyperpolarization and stimulation of basal rates of L‐arginine transport and NO biosynthesis.