Evidence for the Expression of Multiple Uracil Nucleotide‐Stimulated P2 Receptors Coupled to Smooth Muscle Contraction in Porcine Isolated Arteries

<jats:sec><jats:title>Background and purpose:</jats:title><jats:p>The uracil nucleotides UDP and UTP have been reported to activate P2Y<jats:sub>2</jats:sub>, P2Y<jats:sub>4</jats:sub> and P2Y<jats:sub>6</jats:sub> receptors to cause vasoconstriction. We have performed a comparative analysis of these receptors in endothelium‐denuded smooth muscle from porcine isolated coronary and ear arteries, using pharmacological and molecular tools.</jats:p></jats:sec><jats:sec><jats:title>Experimental approach:</jats:title><jats:p>Tissue segments were used to construct non‐cumulative concentration response curves for UTP and UDP, in the absence and presence of the P2 receptor antagonists PPADS or suramin. RT‐PCR and immunoblot analyses were employed to define gene expression and immunoreactivity for P2Y<jats:sub>2</jats:sub>, P2Y<jats:sub>4</jats:sub> and P2Y<jats:sub>6</jats:sub> receptors.</jats:p></jats:sec><jats:sec><jats:title>Key results:</jats:title><jats:p>In the coronary artery, UTP‐evoked contractile responses were reduced in the presence of suramin, but not PPADS, while the smaller responses to UDP were unaffected by either antagonist. In the ear artery, contractile responses to UDP were much smaller than those to UTP; responses to UTP were inhibited by both PPADS and suramin. RT‐PCR suggested predominant expression of P2Y<jats:sub>2</jats:sub> receptors in the coronary artery, while P2Y<jats:sub>4</jats:sub> and P2Y<jats:sub>6</jats:sub> receptor gene expression appeared equivalent in both tissues. Immunoblot analyses provided evidence for P2Y<jats:sub>6</jats:sub> receptors in both tissues, with equivocal evidence of P2Y<jats:sub>2</jats:sub> and P2Y<jats:sub>4</jats:sub> receptor immunoreactivities.</jats:p></jats:sec><jats:sec><jats:title>Conclusions and implications:</jats:title><jats:p>We conclude that UTP‐evoked contraction of porcine coronary artery smooth muscle appears to be predominantly P2Y<jats:sub>2</jats:sub>‐mediated, while the ear artery appears to express a uracil nucleotide‐sensitive P2 receptor(s) which fails to fit readily into the current classification.</jats:p><jats:p><jats:italic>British Journal of Pharmacology</jats:italic> (2007) <jats:bold>150</jats:bold>, 604–612. doi:<jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" xlink:href="10.1038/sj.bjp.0707120">10.1038/sj.bjp.0707120</jats:ext-link></jats:p></jats:sec>