Piglet saphenous vein contains multiple relaxatory prostanoid receptors: evidence for EP 4 , EP 2 , DP and IP receptor subtypes

1 Prostaglandin E 2 produced endothelium‐independent relaxation of phenylephrine‐ and 5‐HT‐contracted piglet saphenous vein (PSV; pEC 50 =8.6±0.2; n =6). 2 The prostanoid EP 4 receptor antagonist GW627368X (30–300 n M ) produced parallel rightward displacement of PGE 2 concentration–effect ( E /[A]) curves (p K b =9.2±0.2; slope=1). Higher concentrations of GW627368X did not produce further rightward shifts, revealing the presence of non‐EP 4 prostanoid receptors. 3 In all, 18 other prostanoid receptor agonists relaxed PSV in a concentration‐related manner. Relative potencies of agonists most sensitive to 10  μ M GW627368X (and therefore predominantly activating EP 4 receptors) correlated well with those at human recombinant EP 4 receptors in human embryonic kidney (HEK‐293) cells ( r 2 =0.74). 4 In the presence of 10  μ M GW627368X, the rank order of agonist relative potency matched that of the human recombinant EP 2 receptor in Chinese hamster ovary cells ( r 2 =0.72). 5 Iloprost, cicaprost and PGI 2 relaxed PSV maximally and were antagonised by 10  μ M GW627368X, demonstrating that they were full EP 4 receptor agonists. Residual responses to these compounds in the presence of GW627368X suggested the presence of IP receptors. 6 BW245C relaxed PSV maximally (pEC 50 =6.8±0.1). In the presence of 10  μ M GW627368X, BW245C produced biphasic E /[A] curves (phase one pEC 50 =6.6; α =24%; phase two pEC 50 =5.1; α =112%). Phase two was antagonised by the DP receptor antagonist BW A868C (1  μ M ), demonstrating that BW245C is an agonist at DP and EP4 receptors. 7 We conclude that PSV contains EP 4 , EP 2 , DP and IP receptors; IP receptor agonists are also porcine EP 4 receptor agonists.British Journal of Pharmacology (2005) 144 , 405–415. doi: 10.1038/sj.bjp.0706088