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The aim of this study, therefore, was to use subtype-selective antagonists to determine the roles of individual P2Y receptor subtypes in nucleotide-evoked pulmonary vasodilation and vasoconstriction. Isometric tension was recorded from rat intrapulmonary artery rings (i.d. 200\u2013500\u00a0\u00b5m) mounted on a wire myograph. Nucleotides evoked concentration- and endothelium-dependent vasodilation of precontracted tissues, but the concentration\u2013response curves were shallow and did not reach a plateau. The selective P2Y<jats:sub>2<\/jats:sub> antagonist, AR-C118925XX, inhibited uridine 5\u2032-triphosphate (UTP)- but not adenosine 5\u2032-triphosphate (ATP)-evoked relaxation, whereas the P2Y<jats:sub>6<\/jats:sub> receptor antagonist, MRS2578, had no effect on UTP but inhibited relaxation elicited by uridine 5\u2032-diphosphate (UDP). ATP-evoked relaxations were unaffected by the P2Y<jats:sub>1<\/jats:sub> receptor antagonist, MRS2179, which substantially inhibited responses to adenosine 5\u2032-diphosphate (ADP), and by the P2Y<jats:sub>12\/13<\/jats:sub> receptor antagonist, cangrelor, which potentiated responses to ADP. Both agonists were unaffected by CGS1593, an adenosine receptor antagonist. Finally, AR-C118925XX had no effect on vasoconstriction elicited by UTP or ATP at resting tone, although P2Y<jats:sub>2<\/jats:sub> receptor mRNA was extracted from endothelium-denuded tissues using reverse transcription polymerase chain reaction with specific oligonucleotide primers. In conclusion, UTP elicits pulmonary vasodilation via P2Y<jats:sub>2<\/jats:sub> receptors, whereas UDP acts at P2Y<jats:sub>6<\/jats:sub> and ADP at P2Y<jats:sub>1<\/jats:sub> receptors, respectively. How ATP induces vasodilation is unclear, but it does not involve P2Y<jats:sub>1<\/jats:sub>, P2Y<jats:sub>2<\/jats:sub>, P2Y<jats:sub>12<\/jats:sub>, P2Y<jats:sub>13<\/jats:sub>, or adenosine receptors. UTP- and ATP-evoked vasoconstriction was not mediated by P2Y<jats:sub>2<\/jats:sub> receptors. Thus, this study advances our understanding of how nucleotides modulate pulmonary vascular tone.<\/jats:p>","DOI":"10.1007\/s11302-022-09895-x","type":"journal-article","created":{"date-parts":[[2022,8,26]],"date-time":"2022-08-26T04:02:52Z","timestamp":1661486572000},"page":"515-528","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Characterisation of P2Y receptor subtypes mediating vasodilation and vasoconstriction of rat pulmonary artery using selective antagonists"],"prefix":"10.1007","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8887-6351","authenticated-orcid":false,"given":"Markie O.","family":"Dales","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Callum","family":"Mitchell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8821-1088","authenticated-orcid":false,"given":"Alison M.","family":"Gurney","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0003-609X","authenticated-orcid":false,"given":"Robert M.","family":"Drummond","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9661-5437","authenticated-orcid":false,"given":"Charles","family":"Kennedy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,8,26]]},"reference":[{"key":"9895_CR1","doi-asserted-by":"publisher","first-page":"1415","DOI":"10.1111\/j.1476-5381.1996.tb15554.x","volume":"118","author":"A Rubino","year":"1996","unstructured":"Rubino A, Burnstock G (1996) Evidence for a P2-purinoceptor mediating vasoconstriction by UTP, ATP and related nucleotides in the isolated pulmonary vascular bed of the rat. 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