Regulation of P2Y1 receptor-mediated signaling by the ectonucleoside triphosphate diphosphohydrolase isozymes NTPDase1 and NTPDase2
| Autor: | José L. Boyer, Claudia P. Alvarado-Castillo, T. Kendall Harden |
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| Rok vydání: | 2004 |
| Předmět: |
P2Y receptor
P2 receptor Biology Astrocytoma Cell Line Substrate Specificity Mice Radioligand Assay Receptors Purinergic P2Y1 Antigens CD Cell Line Tumor Animals Humans Receptor Protease-activated receptor 2 Common gamma chain Insulin-like growth factor 1 receptor Pharmacology Adenosine Triphosphatases Receptors Purinergic P2 Apyrase Molecular biology Coculture Techniques Cell biology Isoenzymes Interleukin 10 Kinetics Type C Phospholipases Molecular Medicine Adenosine A2B receptor Signal Transduction |
| Zdroj: | Molecular pharmacology. 67(1) |
| ISSN: | 0026-895X |
| Popis: | Ectonucleoside triphosphate diphosphohydrolases (NTPDases) control the concentration of released extracellular nucleotides, but the precise physiological roles played by these isozymes in modulation of P2 receptor signaling remain unclear. Activation of the human P2Y 1 receptor was studied in the presence of NTPDase1 or NTPDase2 expressed either in the same cell as the receptor or in P2Y 1 receptor-expressing cells cocultured with NTPDaseexpressing cells. Coexpression of NTPDase1 with the P2Y 1 receptor resulted in increases in the EC 50 for 2′-methylthioadenosine 5′-diphosphate (2MeSADP; 12-fold), ADP (50-fold), and ATP (10-fold) for activation of phospholipase C. Similar effects were observed when the P2Y 1 receptor and NTPDase1 were expressed on different cells. These results are explained by the capacity of NTPDase1 to hydrolyze both nucleoside triphosphates and diphosphates. NTPDase2 preferentially hydrolyzes nucleoside triphosphates, and the presence of NTPDase2 under either coexpression or coculture conditions did not change the EC 50 of 2MeSADP, ADP, or adenosine 5′- O -(2-thiodiphosphate) for activation of the P2Y 1 receptor. However, the EC 50 for ATP was 15-fold lower in the presence of NTPDase2 than in cells expressing the P2Y 1 receptor alone. Whereas expression of NTPDase1 decreased basal activity of the P2Y 1 receptor, the presence of the NTPDase2 resulted in P2Y 1 receptor-dependent increases in basal activity. These results suggest that basal activity of the P2Y 1 receptor is maintained by paracrine or autocrine release of receptor agonists and that the biological and/or pharmacological response mediated by P2Y receptors in target tissues is highly dependent on the types of ectonucleotidases expressed in the vicinity of the receptor. |
| Databáze: | OpenAIRE |
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