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.
Walch
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L
CNRS ESA 8078, 133 av. de la résistance, 92350 Le Plessis-Robinson, France.
de Montpreville
V
V
Brink
C
C
Norel
X
X
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000494:pharmacology; D002227:Carbazoles / Q000494:pharmacology; D046508:Culture Techniques; D012531:Dibenz(b,f)(1,4)oxazepine-10(11H)-carboxylic acid, 8-chloro-, 2-acetylhydrazide / Q000494:pharmacology; D015232:Dinoprostone / Q000031:analogs & derivatives* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000502:physiology; D005260:Female; D006538:Heptanoic Acids / Q000494:pharmacology; D006801:Humans; D016285:Iloprost / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D011448:Prostaglandin Antagonists / Q000494:pharmacology; D011461:Prostaglandins F, Synthetic / Q000494:pharmacology; D011667:Pulmonary Veins / Q000187:drug effects / Q000502:physiology*; D011982:Receptors, Prostaglandin / Q000502:physiology; D018078:Receptors, Prostaglandin E / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*; D058306:Receptors, Prostaglandin E, EP1 Subtype; D058308:Receptors, Prostaglandin E, EP3 Subtype; D017482:Receptors, Thromboxane / Q000037:antagonists & inhibitors / Q000502:physiology*; D013449:Sulfonamides / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects; D014966:Xanthenes / Q000494:pharmacology; D044004:Xanthones
D001713:Biphenyl Compounds; D002227:Carbazoles; D006538:Heptanoic Acids; C545635:PTGER1 protein, human; C545647:PTGER3 protein, human; D011448:Prostaglandin Antagonists; D011461:Prostaglandins F, Synthetic; D011982:Receptors, Prostaglandin; D018078:Receptors, Prostaglandin E; D058306:Receptors, Prostaglandin E, EP1 Subtype; D058308:Receptors, Prostaglandin E, EP3 Subtype; D017482:Receptors, Thromboxane; D013449:Sulfonamides; D014966:Xanthenes; D044004:Xanthones; D012531:Dibenz(b,f)(1,4)oxazepine-10(11H)-carboxylic acid, 8-chloro-, 2-acetylhydrazide; C053876:6-isopropoxy-9-oxoxanthene-2-carboxylic acid; C006326:fluprostenol; C016767:sulprostone; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; C060013:vapiprost; D016285:Iloprost; D015232:Dinoprostone; C063119:ramatroban