Endothelial P2-purinoceptors: subtypes and signal transduction.
1. Adenine nucleotides stimulate the synthesis and release of prostacyclin and nitric oxide (two potent platelet aggregation inhibitors) by endothelial cells from different origins. These responses are mediated by P2 purinergic receptors, coupled to the production of inositol (1,4,5)trisphosphate (InsP3) and to the increase of intracytoplasmic calcium concentration. 2. In bovine aortic endothelial cells (BAEC), both 2-MeSATP and UTP stimulate the production of InsP3. By experiments of additivity and cross desensitization, we have confirmed the expression of both P2Y/P2Y1 and P2U/P2Y2 receptors on these cells. Moreover, these receptors are not segregated on different subpopulations but are co-localized on the same cells. 3. The action of UTP on InsP3 production was inhibited by pertussis toxin and was unaffected by a pretreatment with phorbol 12-myristate, 13-acetate (PMA). On the other hand, the response induced by 2-MeSATP was inhibited by PMA but insensitive to pertussis toxin. These results suggest that P2Y/P2Y1 and P2U/P2Y2 receptors are respectively coupled to Gq/G11 and G1 proteins. 4. Northern blotting experiments revealed the expression of the P2Y1 (doublet of 2 and 2.2 kb) and of the P2Y2 (2.4 kb) receptor messengers in BAEC. A signal corresponding to the P2Y2 mRNA was also detectable in human umbilical vein endothelial cells. 5. These various results thus demonstrate the expression of the P2Y1 and P2Y2 receptors in vascular endothelial cells.
Pirotton
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Institute of Interdisciplinary Research, Faculte de Médecine, Brussels, Belgium.
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D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D015152:Blotting, Northern; D002417:Cattle; D004730:Endothelium, Vascular / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D018048:Receptors, Purinergic P2 / Q000145:classification* / Q000378:metabolism; D058472:Receptors, Purinergic P2Y1; D058473:Receptors, Purinergic P2Y2; D015398:Signal Transduction; D014544:Uridine Triphosphate / Q000494:pharmacology
C546382:P2RY1 protein, human; C546385:P2RY2 protein, human; D018048:Receptors, Purinergic P2; D058472:Receptors, Purinergic P2Y1; D058473:Receptors, Purinergic P2Y2; D015544:Inositol 1,4,5-Trisphosphate; D000255:Adenosine Triphosphate; D014544:Uridine Triphosphate