@article {Lynch1171, author = {Kevin J. Lynch and Edward Touma and Wende Niforatos and Karen L. Kage and Edward C. Burgard and Tim van Biesen and Elizabeth A. Kowaluk and Michael F. Jarvis}, title = {Molecular and Functional Characterization of Human P2X2 Receptors}, volume = {56}, number = {6}, pages = {1171--1181}, year = {1999}, doi = {10.1124/mol.56.6.1171}, publisher = {American Society for Pharmacology and Experimental Therapeutics}, abstract = {P2X receptors are a family of ATP-gated ion channels. Four cDNAs with a high degree of homology to the rat P2X2 receptor were isolated from human pituitary and pancreas RNA. Genomic sequence indicated that these cDNAs represent alternatively spliced messages. Northern analysis revealed high levels of human P2X2(hP2X2) message in the pancreas, and splice variants could be detected in a variety of tissues. Two cDNAs encoded functional ion channels when expressed in Xenopus oocytes, a receptor structurally homologous to the prototype rat P2X2 receptor (called hP2X2a) and a variant containing a deletion within its cytoplasmic C terminus (called hP2X2b). Pharmacologically, these functional human P2X2 receptors were virtually indistinguishable, with the P2X receptor agonists ATP, 2-methylthio-ATP, 2' and 3'-O-(4-benzoylbenzoyl)-ATP, and ATP5'-O-(3-thiotriphosphate) being approximately equipotent (EC50 = 1 μM) in eliciting extracellular Ca2+ influx. The P2 receptor agonists α,β-methylene ATP, adenosine, adenosine 5'-O-(2-thiodiphosphate), and UTP were inactive at concentrations up to 100 μM. Both hP2X2a and hP2X2b receptors were sensitive to the P2 receptor antagonist pyridoxal-5-phosphate-6-azophenyl-2',4'-disulfonic acid (IC50 = 3 μM). In contrast to the analogous rat P2X2 and P2X2b receptors, the desensitization rates of the hP2X2a and hP2X2b receptors were equivalent. Both functional forms of the human P2X2receptors formed heteromeric channels with the human P2X3receptor. These data demonstrate that the gene structure and mRNA heterogeneity of the P2X2 receptor subtype are evolutionarily conserved between rat and human, but also suggest that alternative splicing serves a function other than regulating the desensitization rate of the human receptor.}, issn = {0026-895X}, URL = {https://molpharm.aspetjournals.org/content/56/6/1171}, eprint = {https://molpharm.aspetjournals.org/content/56/6/1171.full.pdf}, journal = {Molecular Pharmacology} }