Characterization of excitatory prostanoid receptors in the human umbilical artery in vitro

1 5-HT and the prostanoid TP receptor agonists, U46619 and I-BOP, constricted the human umbilical artery with pEC(50) values of 7.3 +/- 0.2, 6.7 +/- 0.1, and 7.3 +/- 0.2, respectively. The selective TP receptor antagonist, GR32191 (0.1 mu M), shifted the concentration-effect curves to U46619 and I-BOP to the right, but had no effect on the response to 5-HT. 2 The natural prostaglandins, PGF(2 alpha) and PGE(2), caused concentration-dependent contraction with pEC(50) values of 5.2 +/- 0.2 and 4.9 +/- 0.2, respectively. PGD(2) was a partial agonist with a pEC(50) Of 5.24 +/- 0.03. GR32191 (0.1 mu M) inhibited the responses to all of these compounds suggesting that they produce contraction by acting at TP receptors. 3 Sulprostone failed to elicit contraction in the human umbilical artery at concentrations up to 4.4 mu M suggesting the absence of EP1 and EP3 receptors. Despite this, 17-phenyltrinor PGE(2) and GR63799 both induced contraction at concentrations above I mu M, but the effects were sensitive to GR32191 (0.1 mu M). 4 Fluprostenol had no effect on the human umbilical artery at concentrations up to 17 mu M suggesting the absence of FP receptors. Cloprostenol was ineffective in two tissues, but caused contraction in one tissue at the highest concentration tested (1.7 mu M). However, this response was abolished in the presence of GR32191 (0.1 mu M). 5 The effects of four TP receptor antagonists were assessed by global non-linear regression analysis. GR32191, SQ29548, SQ30741, and ICI1926o5 competitively inhibited responses to U46619 with pK(b) values of 8.0 +/- 0.1, 7.6 +/- 0.1, 7.0 +/- 0.2 and 8.1 +/- 0.1, respectively. 6 These results suggest that the human umbilical artery functionally expresses TP receptors, but not EP1, EP2 or FP receptors.