{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T20:04:05Z","timestamp":1791144245564,"version":"4.1.0"},"reference-count":39,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2009,1,29]],"date-time":"2009-01-29T00:00:00Z","timestamp":1233187200000},"content-version":"vor","delay-in-days":3650,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[1999,2]]},"abstract":"<jats:p>\n<jats:list list-type=\"explicit-label\">\n<jats:list-item><jats:p>The modulatory effects of extracellular H<jats:sup>+<\/jats:sup> and Zn<jats:sup>2+<\/jats:sup> were tested against ATP\u2010responses at rat P2X<jats:sub>4<\/jats:sub> (rP2X<jats:sub>4<\/jats:sub>) receptors expressed in <jats:italic>Xenopus<\/jats:italic> oocytes under voltage\u2010clamp conditions.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>ATP (0.1\u2013100\u2003\u03bc<jats:sc>M<\/jats:sc>, at pH\u20037.5), evoked inward currents <jats:italic>via<\/jats:italic> rP2X<jats:sub>4<\/jats:sub> receptors (EC<jats:sub>50<\/jats:sub> value, 4.1\u00b10.98\u2003\u03bc<jats:sc>M<\/jats:sc>; n<jats:sub>H<\/jats:sub>, 1.2\u00b10.1). ATP potency was reduced 2 fold, at pH\u20036.5, without altering maximal activity. ATP potency was reduced by a further 4 fold, at pH\u20035.5, and the maximal activity of ATP was also reduced. Alkaline conditions (pH\u20038.0) had no effect on ATP\u2010responses.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Zn<jats:sup>2+<\/jats:sup> (100\u2003n<jats:sc>M<\/jats:sc>\u201310\u2003\u03bc<jats:sc>M<\/jats:sc>) potentiated ATP\u2010responses at the rP2X<jats:sub>4<\/jats:sub> receptor by 2 fold, whereas higher concentrations (30\u2003\u03bc<jats:sc>M<\/jats:sc>\u20131\u2003m<jats:sc>M<\/jats:sc>) inhibited ATP\u2010responses. Zn<jats:sup>2+<\/jats:sup> potentiation was due to an increase in ATP potency, whereas its inhibitory action was due to a reduction in ATP efficacy.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Zn<jats:sup>2+<\/jats:sup> modulation of ATP\u2010responses was pH\u2010dependent. At pH\u20036.5, the bell\u2010shaped curve for Zn<jats:sup>2+<\/jats:sup> was shifted to the right by 1 log unit. At pH\u20035.5, Zn<jats:sup>2+<\/jats:sup> potentiation was abolished and its inhibitory effect reduced considerably.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Suramin (50\u2003\u03bc<jats:sc>M<\/jats:sc>) also potentiated ATP\u2010responses at rP2X<jats:sub>4<\/jats:sub> receptors. Neither H<jats:sup>+<\/jats:sup> (pH\u20036.5 and 5.5), Zn<jats:sup>2+<\/jats:sup> (10\u2013100\u2003\u03bc<jats:sc>M<\/jats:sc>) or a combination of both failed to reveal an inhibitory action of suramin at rP2X<jats:sub>4<\/jats:sub> receptors.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>In conclusion, H<jats:sup>+<\/jats:sup> and Zn<jats:sup>2+<\/jats:sup> exerted opposite effects on the rP2X<jats:sub>4<\/jats:sub> receptor by lowering and raising agonist potency, respectively. H<jats:sup>+<\/jats:sup> (3\u2003\u03bc<jats:sc>M<\/jats:sc>) and Zn<jats:sup>2+<\/jats:sup> (30\u2003\u03bc<jats:sc>M<\/jats:sc>) also reduces agonist efficacy by lowering the number of rP2X<jats:sub>4<\/jats:sub> receptors available for activation. The striking differences between the modulatory actions of H<jats:sup>+<\/jats:sup> and Zn<jats:sup>2+<\/jats:sup> at rP2X<jats:sub>4<\/jats:sub> and rP2X<jats:sub>2<\/jats:sub> receptors are discussed.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic> (1999) <jats:bold>126<\/jats:bold>, 762\u2013768; doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0702325\">10.1038\/sj.bjp.0702325<\/jats:ext-link><\/jats:p>","DOI":"10.1038\/sj.bjp.0702325","type":"journal-article","created":{"date-parts":[[2005,1,28]],"date-time":"2005-01-28T19:41:09Z","timestamp":1106941269000},"page":"762-768","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":66,"title":["Modulation of ATP\u2010responses at recombinant rP2X<sub>4<\/sub> receptors by extracellular pH and zinc"],"prefix":"10.1111","volume":"126","author":[{"given":"S S","family":"Wildman","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B F","family":"King","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G","family":"Burnstock","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2009,1,29]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/308734a0"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1996.tb16070.x"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.17-14-05297.1997"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(95)01203-Q"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/371519a0"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(92)90183-8"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1996.tb00333.x"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/0301-0082(90)90034-E"},{"key":"e_1_2_7_10_1","first-page":"44P","article-title":"Extracellular acidification inhibits current flow through human P2X4 receptors expressed in Xenopus oocytes","volume":"506","author":"CLARKE C.E.","year":"1998","journal-title":"J. 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