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As <jats:italic>iso<\/jats:italic>prostanes are isomeric with prostaglandins, PGE<jats:sub>2<\/jats:sub> and sulprostone (a selective EP<jats:sub>3<\/jats:sub>\u2010receptor agonist) were examined in parallel.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>8\u2010<jats:italic>Iso<\/jats:italic>\u2010PGE<jats:sub>1<\/jats:sub>, 8\u2010<jats:italic>iso<\/jats:italic>\u2010PGE<jats:sub>2<\/jats:sub> (0.1 n<jats:sc>M<\/jats:sc>\u20131 <jats:italic>\u03bc<\/jats:italic><jats:sc>M<\/jats:sc>), sulprostone (1 n<jats:sc>M<\/jats:sc>\u20131 <jats:italic>\u03bc<\/jats:italic><jats:sc>M<\/jats:sc>) and PGE<jats:sub>2<\/jats:sub> (1 <jats:italic>\u03bc<\/jats:italic><jats:sc>M<\/jats:sc>) suppressed EFS\u2010evoked [<jats:sup>3<\/jats:sup>H]ACh release from guinea\u2010pig trachea in a concentration\u2010dependent manner, producing 39.5, 53.9, 61.2 and 59.9% inhibition, respectively, at 1 <jats:italic>\u03bc<\/jats:italic><jats:sc>M<\/jats:sc>. It should be noted that an established maximum effective concentration was not determined.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Neither SQ 29,548 (1 <jats:italic>\u03bc<\/jats:italic><jats:sc>M<\/jats:sc>; a TP\u2010receptor antagonist) nor AH 6809 (10 <jats:italic>\u03bc<\/jats:italic><jats:sc>M<\/jats:sc>; an EP<jats:sub>1<\/jats:sub>\u2010\/EP<jats:sub>2<\/jats:sub>\u2010\/DP\u2010receptor antagonist) reversed the inhibitory effect of these compounds.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>L\u2010798,106, a novel and highly selective EP<jats:sub>3<\/jats:sub>\u2010receptor antagonist, produced a parallel shift to the right of the concentration\u2013response curves that described the inhibitory action of sulprostone on EFS\u2010evoked contractile responses in guinea\u2010pig vas deferens (an established EP<jats:sub>3<\/jats:sub>\u2010receptor\u2010expressing tissue), from which a mean p<jats:italic>A<\/jats:italic><jats:sub>2<\/jats:sub> of 7.48 was derived. On guinea\u2010pig trachea, L\u2010798,106 also antagonised sulprostone\u2010induced inhibition of EFS\u2010induced twitch responses, with similar potency (mean p<jats:italic>A<\/jats:italic><jats:sub>2<\/jats:sub>=7.82).<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The inhibitory effects of 8\u2010<jats:italic>iso<\/jats:italic>\u2010PGE<jats:sub>1<\/jats:sub>, 8\u2010<jats:italic>iso<\/jats:italic>\u2010PGE<jats:sub>2<\/jats:sub>, sulprostone and PGE<jats:sub>2<\/jats:sub> on EFS\u2010induced [<jats:sup>3<\/jats:sup>H]ACh release was blocked by L\u2010798,106 at a concentration (10 <jats:italic>\u03bc<\/jats:italic><jats:sc>M<\/jats:sc>) that binds only weakly to human recombinant EP<jats:sub>1<\/jats:sub>\u2010, EP<jats:sub>2<\/jats:sub>\u2010 and EP<jats:sub>4<\/jats:sub>\u2010receptor subtypes expressed in HEK 293 cells.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>These data suggest that E\u2010ring 8\u2010<jats:italic>iso<\/jats:italic>prostanes, PGE<jats:sub>2<\/jats:sub> and sulprostone inhibit EFS\u2010evoked [<jats:sup>3<\/jats:sup>H]ACh release from cholinergic nerves innervating guinea\u2010pig trachea, by interacting with prejunctional prostanoid receptors of the EP<jats:sub>3<\/jats:sub>\u2010subtype.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic> (2004) <jats:bold>141<\/jats:bold>, 600\u2013609. doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0705648\">10.1038\/sj.bjp.0705648<\/jats:ext-link><\/jats:p>","DOI":"10.1038\/sj.bjp.0705648","type":"journal-article","created":{"date-parts":[[2004,2,19]],"date-time":"2004-02-19T18:17:58Z","timestamp":1077214678000},"page":"600-609","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["E\u2010Ring 8\u2010<i>iso<\/i>prostanes inhibit ACh release from parasympathetic nerves innervating guinea\u2010pig trachea through agonism of prostanoid receptors of the EP<sub>3<\/sub>\u2010subtype"],"prefix":"10.1111","volume":"141","author":[{"given":"Deborah L","family":"Clarke","sequence":"first","affiliation":[]},{"given":"Mark A","family":"Giembycz","sequence":"additional","affiliation":[]},{"given":"Hema J","family":"Patel","sequence":"additional","affiliation":[]},{"given":"Maria G","family":"Belvisi","sequence":"additional","affiliation":[]}],"member":"311","published-online":{"date-parts":[[2009,1,30]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1007560025570"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.1992.72.3.699"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.93.06030328"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1471-4892(02)00145-5"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1996.tb15300.x"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.pharmtox.41.1.661"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0703012"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/0090-6980(94)90084-1"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/0090-6980(85)90096-6"},{"key":"e_1_2_7_11_1","first-page":"467","article-title":"New evidence with selective agonists and antagonists for the subclassification of PGE2\u2010sensitive (EP) receptors","volume":"17","author":"COLEMAN R.A.","year":"1987","journal-title":"Adv. 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