Prostanoid EP(1)- and TP-receptors involved in the contraction of human pulmonary veins.

1. To characterize the prostanoid receptors (TP, FP, EP(1) and/or EP(3)) involved in the vasoconstriction of human pulmonary veins, isolated venous preparations were challenged with different prostanoid-receptor agonists in the absence or presence of selective antagonists. 2. The stable thromboxane A(2) mimetic, U46619, was a potent constrictor agonist on human pulmonary veins (pEC(50)=8.60+/-0.11 and E(max)=4.61+/-0.46 g; n=15). The affinity values for two selective TP-antagonists (BAY u3405 and GR32191B) versus U46619 were BAY u3405: pA(2)=8.94+/-0.23 (n=3) and GR32191B: apparent pK(B)=8.25+/-0.34 (n=3), respectively. These results are consistent with the involvement of TP-receptor in the U46619 induced contractions. 3. The two EP(1)-/EP(3)- agonists (17-phenyl-PGE(2) and sulprostone) induced contraction of human pumonary veins (pEC(50)=8.56+/-0.18; E(max)=0.56+/-0.24 g; n=5 and pEC(50)=7.65+/-0.13; E(max)=1.10+/-0.12 g; n=14, respectively). The potency ranking for these agonists: 17-phenyl-PGE(2) > sulprostone suggests the involvement of an EP(1)-receptor rather than EP(3). In addition, the contractions induced by sulprostone, 17-phenyl-PGE(2) and the IP-/EP(1)- agonist (iloprost) were blocked by the DP-/EP(1)-/EP(2)-receptor antagonist (AH6809) as well as by the EP(1) antagonist (SC19220). 4. PGF(2alpha) induced small contractions which were blocked by AH6809 while fluprostenol was ineffective. These results indicate that FP-receptors are not implicated in the contraction of human pulmonary veins. 5. These data suggest that the contractions induced by prostanoids involved TP- and EP(1)-receptors in human pulmonary venous smooth muscle.