Pharmacological characterization of prostanoid receptors mediating vasoconstriction in human umbilical vein.

1. This study was undertaken to characterize pharmacologically the prostanoid receptor subtypes mediating contraction in human umbilical vein (HUV). 2. HUV rings were mounted in organ baths and concentration-response curves to U-46619 (TXA(2) mimetic) were constructed in the absence or presence of SQ-29548 or ICI-192,605 (TP receptor antagonists). U-46619 was a potent constrictor (pEC(50): 8.03). SQ-29548 and ICI-192,605 competitively antagonized responses to U-46619 with pK(B) values of 7.96 and 9.07, respectively. 3. Concentration-response curves to EP receptor agonists: PGE(2), misoprostol and 17-phenyl-trinor-PGE(2) gave pEC(50) values of 5.06, 5.25 and 5.32, respectively. Neither pEC(50) nor maximum of PGE(2) and 17-phenyl-trinor-PGE(2) concentration-response curves were modified by the DP/EP(1)/EP(2) receptor antagonist AH 6809 (1 micro M). However, ICI-192,605 produced a concentration-dependent antagonism of the responses to all the EP receptor agonists. The pA(2) estimated for ICI-192,605 against PGE(2) or misoprostol were 8.91 and 9.22, respectively. 4. Concentration-response curves to FP receptor agonists: PGF(2)(alpha) and fluprostenol gave pEC(50) values of 6.20 and 5.82, respectively. ICI-192,605 (100 nM) was completely ineffective against PGF(2)(alpha) or fluprostenol. In addition, lack of antagonistic effect of AH 6809 (1 micro M) against PGF(2)(alpha) was observed. 5. In conclusion, the findings obtained with TP-selective agonist and antagonists provide strong evidence of the involvement of TP receptors promoting vasoconstriction in HUV. Furthermore, the action of the natural and synthetic EP receptor agonists appears to be mediated via TP receptors. On the other hand, the results employing FP receptor agonists and antagonists of different prostanoid receptors suggest the presence of FP receptors mediating vasoconstriction in this vessel.