Activation of A2-purinoceptors by adenosine stimulates L-arginine transport (system y+) and nitric oxide synthesis in human fetal endothelial cells.
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.
Sobrevia
L
L
Vascular Biology Research Centre, King's College, London, UK. l.sobrevia@kcl.ac.uk
Yudilevich
D L
DL
Mann
G E
GE
D000241:Adenosine / Q000494:pharmacology*; D001120:Arginine / Q000378:metabolism*; D001692:Biological Transport / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004727:Endothelium / Q000378:metabolism; D005333:Fetus / Q000378:metabolism*; D006801:Humans; D019001:Nitric Oxide Synthase / Q000096:biosynthesis*; D011983:Receptors, Purinergic / Q000187:drug effects* / Q000502:physiology*
D011983:Receptors, Purinergic; D001120:Arginine; D019001:Nitric Oxide Synthase; D000241:Adenosine