{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,7,25]],"date-time":"2024-07-25T16:02:59Z","timestamp":1721923379833},"reference-count":38,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2009,1,30]],"date-time":"2009-01-30T00:00:00Z","timestamp":1233273600000},"content-version":"vor","delay-in-days":2221,"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":[[2003,1]]},"abstract":"<jats:p>\n<jats:list list-type=\"explicit-label\">\n<jats:list-item><jats:p>In PC12 cells, adenine nucleotides inhibit voltage\u2010activated Ca<jats:sup>2+<\/jats:sup> currents and adenylyl cyclase activity, and the latter effect was reported to involve P2Y<jats:sub>12<\/jats:sub> receptors. To investigate whether these two effects are mediated by one P2Y receptor subtype, we used the antithrombotic agents 2\u2010methylthio\u2010AMP (2\u2010MeSAMP) and N<jats:sup>6<\/jats:sup>\u2010(2\u2010methyl\u2010thioethyl)\u20102\u2010(3,3,3\u2010trifluoropropylthio)\u2010\u03b2,\u03b3\u2010dichloromethylene\u2010ATP (AR\u2010C69931MX).<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>ADP reduced A<jats:sub>2A<\/jats:sub> receptor\u2010dependent cyclic AMP synthesis with half maximal effects at 0.1\u20130.17 \u03bc<jats:sc>M<\/jats:sc>. In the presence of 30 \u03bc<jats:sc>M<\/jats:sc> 2\u2010MeSAMP or 100 n<jats:sc>M<\/jats:sc> AR\u2010C69931MX, concentration response curves were shifted to the right by factors of 39 and 30, indicative of pA<jats:sub>2<\/jats:sub> values of 6.1 and 8.5, respectively.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The inhibition of Ca<jats:sup>2+<\/jats:sup> currents by ADP was attenuated by 10\u20131000 n<jats:sc>M<\/jats:sc> AR\u2010C69931MX and by 3\u2013300 \u03bc<jats:sc>M<\/jats:sc> 2\u2010MeSAMP. ADP reinhibited Ca<jats:sup>2+<\/jats:sup> currents after removal of 2\u2010MeSAMP within less than 15 s, but required 2 min to do so after removal of AR\u2010C69931MX.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>ADP inhibited Ca<jats:sup>2+<\/jats:sup> currents with half maximal effects at 5\u201320 \u03bc<jats:sc>M<\/jats:sc>. AR\u2010C69931MX (10\u2013100 n<jats:sc>M<\/jats:sc>) displaced concentration response curves to the right, and the resulting Schild plot showed a slope of 1.09 and an estimated <jats:italic>pK<jats:sub>B<\/jats:sub><\/jats:italic> value of 8.7. Similarly, 10\u2013100 \u03bc<jats:sc>M<\/jats:sc> 2\u2010MeSAMP also caused rightward shifts resulting in a Schild plot with a slope of 0.95 and an estimated <jats:italic>pK<jats:sub>B<\/jats:sub><\/jats:italic> of 5.4.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The inhibition of Ca<jats:sup>2+<\/jats:sup> currents by 2\u2010methylthio\u2010ADP and ADP\u03b2S was also antagonized by AR\u2010C69931MX, which (at 30 n<jats:sc>M<\/jats:sc>) caused a rightward shift of the concentration response curve for ADP\u03b2S by a factor of 3.8, indicative of a pA<jats:sub>2<\/jats:sub> value of 8.1.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>These results show that antithrombotic drugs antagonize the inhibition of neuronal Ca<jats:sup>2+<\/jats:sup> channels by adenine nucleotides, which suggests that this effect is mediated by P2Y<jats:sub>12<\/jats:sub> receptors.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic> (2003) <jats:bold>138<\/jats:bold>, 343\u2013350. doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0705037\">10.1038\/sj.bjp.0705037<\/jats:ext-link><\/jats:p>","DOI":"10.1038\/sj.bjp.0705037","type":"journal-article","created":{"date-parts":[[2003,2,8]],"date-time":"2003-02-08T17:22:02Z","timestamp":1044724922000},"page":"343-350","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Attenuation of the P2Y receptor\u2010mediated control of neuronal Ca<sup>2+<\/sup> channels in PC12 cells by antithrombotic drugs"],"prefix":"10.1111","volume":"138","author":[{"given":"Helmut","family":"Kubista","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefan G","family":"Lechner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angelika M","family":"Wolf","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefan","family":"Boehm","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2009,1,30]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0028-3908(99)00141-0"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1959.tb00928.x"},{"key":"e_1_2_7_4_1","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1523\/JNEUROSCI.19-02-00737.1999","article-title":"ATP stimulates sympathetic transmitter release via presynaptic P2X purinoceptors","volume":"19","author":"BOEHM S.","year":"1999","journal-title":"J. Neurosci."},{"key":"e_1_2_7_5_1","doi-asserted-by":"crossref","first-page":"4596","DOI":"10.1523\/JNEUROSCI.16-15-04596.1996","article-title":"Involvement of a phorbol esterinsensitive protein kinase C in the \u03b12\u2010adrenergic inhibition of voltage\u2010gated Ca2+ current in chick sympathetic neurons","volume":"16","author":"BOEHM S.","year":"1996","journal-title":"J. Neurosci."},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1124\/pr.54.1.43"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0701880"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-1838(00)00150-8"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.cellbio.16.1.521"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.270.44.26152"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M105912200"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.51.31969"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.270.52.30849"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1978.235.3.C97"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0703185"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI12242"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0037-1616220"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.73.7.2424"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-6147(00)01885-X"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/PL00005101"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/0166-2236(94)90157-0"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/35051599"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0037-1614427"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0704114"},{"key":"e_1_2_7_25_1","first-page":"32","article-title":"Determination of adenylyl cyclase catalytic activity using single and double column procedures","volume":"238","author":"JOHNSON R.A.","year":"1994","journal-title":"Methods Enzymol."},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.16-23-07557.1996"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111803200"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.11.5113"},{"key":"e_1_2_7_29_1","first-page":"413","article-title":"Receptors for purines and pyrimidines","volume":"50","author":"RALEVIC V.","year":"1998","journal-title":"Pharmacol. Rev."},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm980657j"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0703816"},{"key":"e_1_2_7_32_1","first-page":"432","article-title":"Molecular cloning of the platelet P2TAC receptor: pharmacological comparison with another ADP receptor, the P2Y1 receptor","volume":"60","author":"TAKASAKI J.","year":"2001","journal-title":"Mol. Pharmacol."},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1995.1798"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V98.12.3340"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0704514"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1460-9568.2001.01461.x"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0959-4388(98)80060-3"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M009718200"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.301.2.705"}],"container-title":["British Journal of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1038%2Fsj.bjp.0705037","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1038%2Fsj.bjp.0705037","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1038\/sj.bjp.0705037","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,13]],"date-time":"2023-10-13T17:31:18Z","timestamp":1697218278000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1038\/sj.bjp.0705037"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2003,1]]},"references-count":38,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2003,1]]}},"alternative-id":["10.1038\/sj.bjp.0705037"],"URL":"https:\/\/doi.org\/10.1038\/sj.bjp.0705037","archive":["Portico"],"relation":{},"ISSN":["0007-1188","1476-5381"],"issn-type":[{"value":"0007-1188","type":"print"},{"value":"1476-5381","type":"electronic"}],"subject":[],"published":{"date-parts":[[2003,1]]},"assertion":[{"value":"2009-01-30","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}