Biochem Biophys Res Commun 1996 Mar 07;2201:196-202. doi: 10.1006/bbrc.1996.0380.

Cloning and pharmacological characterization of a fourth P2X receptor subtype widely expressed in brain and peripheral tissues including various endocrine tissues.

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We have isolated cDNA encoding a fourth member (P2X-4) of the ATP receptor P2X receptor family from a rat pancreatic islet cDNA library. Rat P2X-4 is a protein of 388 amino acids which shares 50%, 49%, and 47% identity with P2X-1, P2X-2, and P2X-3, respectively, and has two putative transmembrane segments. Rat P2X-4 mRNA is widely expressed in brain and peripheral tissues, including various endocrine tissues, and it is also expressed in various hormone-secreting cell lines. We have heterologously expressed the cloned P2X-4 in Xenopus laevis oocytes and have characterized its pharmacological properties. ATP, its analogs and ADP activate cation-selective ion channels. The order of agonist potency is ATP ADP 2-methyl- thioATP(2MeSATP) >> alpha beta-methelene-ATP (alpha betameATP). ATP-evoked currents are only partially blocked by suramin, reactive blue-2, or H2DIDS. The present study suggests that P2X-4, with pharmacological properties distinct from those of P2X-1+, P2X-2, and P2X-3, mediates extracellular ATP-induced biological effects in non-neuronal cells, including endocrine cells, as well as in neuronal cells.

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