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This study investigated whether<jats:styled-content style=\"fixed-case\">P2Y<jats:sub>14<\/jats:sub><\/jats:styled-content>receptors were functionally expressed in porcine isolated pancreatic arteries.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>Pancreatic arteries were prepared for isometric tension recording and<jats:styled-content style=\"fixed-case\">UDP<\/jats:styled-content>\u2010glucose,<jats:styled-content style=\"fixed-case\">UDP<\/jats:styled-content>and<jats:styled-content style=\"fixed-case\">MRS2690<\/jats:styled-content>were applied cumulatively after preconstriction with<jats:styled-content style=\"fixed-case\">U46619<\/jats:styled-content>, a<jats:styled-content style=\"fixed-case\">TxA<jats:sub>2<\/jats:sub><\/jats:styled-content>mimetic. Levels of phosphorylated myosin light chain 2 (<jats:styled-content style=\"fixed-case\">MLC2<\/jats:styled-content>) were assessed with<jats:styled-content style=\"fixed-case\">W<\/jats:styled-content>estern blotting.<jats:styled-content style=\"fixed-case\">cAMP<\/jats:styled-content>concentrations were assessed using a competitive enzyme immunoassay kit.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>Concentration\u2010dependent contractions with a rank order of potency of<jats:styled-content style=\"fixed-case\">MRS2690<\/jats:styled-content>(10\u2010fold) &gt;<jats:styled-content style=\"fixed-case\">UDP<\/jats:styled-content>\u2010glucose \u2265<jats:styled-content style=\"fixed-case\">UDP<\/jats:styled-content>were recorded. These contractions were reduced by<jats:styled-content style=\"fixed-case\">PPTN<\/jats:styled-content>{4\u2010[4\u2010(piperidin\u20104\u2010yl)phenyl]\u20107\u2010[4\u2010(trifluoromethyl)phenyl]\u20102\u2010naphthoic acid}, a selective antagonist of<jats:styled-content style=\"fixed-case\">P2Y<jats:sub>14<\/jats:sub><\/jats:styled-content>receptors, which did not affect responses to UTP. Contraction to<jats:styled-content style=\"fixed-case\">UDP<\/jats:styled-content>\u2010glucose was not affected by<jats:styled-content style=\"fixed-case\">MRS2578<\/jats:styled-content>, a<jats:styled-content style=\"fixed-case\">P2Y<jats:sub>6<\/jats:sub><\/jats:styled-content>receptor selective antagonist. Raising<jats:styled-content style=\"fixed-case\">cAMP<\/jats:styled-content>levels and forskolin, in the presence of U46619, enhanced contractions to<jats:styled-content style=\"fixed-case\">UDP<\/jats:styled-content>\u2010glucose. In addition,<jats:styled-content style=\"fixed-case\">UDP<\/jats:styled-content>\u2010glucose and<jats:styled-content style=\"fixed-case\">MRS2690<\/jats:styled-content>inhibited forskolin\u2010stimulated<jats:styled-content style=\"fixed-case\">cAMP<\/jats:styled-content>levels. Removal of the endothelium and inhibition of endothelium\u2010derived contractile agents (<jats:styled-content style=\"fixed-case\">TxA<jats:sub>2<\/jats:sub><\/jats:styled-content>,<jats:styled-content style=\"fixed-case\">PGF<jats:sub>2\u03b1<\/jats:sub><\/jats:styled-content>and endothelin\u20101) inhibited contractions to UDP glucose.<jats:styled-content style=\"fixed-case\">Y<\/jats:styled-content>\u201027632, nifedipine and thapsigargin also reduced contractions to the agonists.<jats:styled-content style=\"fixed-case\">UDP<\/jats:styled-content>\u2010glucose and<jats:styled-content style=\"fixed-case\">MRS2690<\/jats:styled-content>increased<jats:styled-content style=\"fixed-case\">MLC2<\/jats:styled-content>phosphorylation, which was blocked by<jats:styled-content style=\"fixed-case\">PPTN<\/jats:styled-content>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Implications<\/jats:title><jats:p><jats:styled-content style=\"fixed-case\">P2Y<jats:sub>14<\/jats:sub><\/jats:styled-content>receptors play a novel vasocontractile role in porcine pancreatic arteries, mediating contraction via<jats:styled-content style=\"fixed-case\">cAMP<\/jats:styled-content>\u2010dependent mechanisms, elevation of intracellular<jats:styled-content style=\"fixed-case\">Ca<jats:sup>2<\/jats:sup><\/jats:styled-content><jats:sup>+<\/jats:sup>levels, activation of<jats:styled-content style=\"fixed-case\">RhoA<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">ROCK<\/jats:styled-content>signalling and<jats:styled-content style=\"fixed-case\">MLC2<\/jats:styled-content>, along with release of<jats:styled-content style=\"fixed-case\">TxA<jats:sub>2<\/jats:sub><\/jats:styled-content>,<jats:styled-content style=\"fixed-case\">PGF<jats:sub>2\u03b1<\/jats:sub><\/jats:styled-content>and endothelin\u20101.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.12473","type":"journal-article","created":{"date-parts":[[2013,10,21]],"date-time":"2013-10-21T08:50:44Z","timestamp":1382345444000},"page":"701-713","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Novel vasocontractile role of the<scp>P2Y<sub>14<\/sub><\/scp>receptor: characterization of its signalling in porcine isolated pancreatic arteries"],"prefix":"10.1111","volume":"171","author":[{"given":"M","family":"Alsaqati","sequence":"first","affiliation":[{"name":"Life Sciences University of Nottingham Nottingham UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M L","family":"Latif","sequence":"additional","affiliation":[{"name":"Life Sciences University of Nottingham Nottingham UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S L F","family":"Chan","sequence":"additional","affiliation":[{"name":"Life Sciences University of Nottingham Nottingham UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"V","family":"Ralevic","sequence":"additional","affiliation":[{"name":"Life Sciences University of Nottingham Nottingham UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2014,1,13]]},"reference":[{"key":"e_1_2_8_2_1","unstructured":"AbbasZ LatifL RalevicV(2011).Effects of P2Y14receptor agonists UDP\u2010glucose and MRS2690 on porcine coronary artery contractility. 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