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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.
Author(s) -
Sobrevia L,
Yudilevich D L,
Mann G E
Publication year - 1997
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.1997.sp021916
Subject(s) - adenosine , cgs 21680 , adenosine a1 receptor , medicine , endocrinology , adenosine receptor , purinergic receptor , hyperpolarization (physics) , agonist , purinergic signalling , biology , adenosine a3 receptor , chemistry , receptor , biochemistry , nuclear magnetic resonance spectroscopy , organic chemistry
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.