Vasorelaxation induced by prostaglandin E2 in human pulmonary vein: role of the EP4 receptor subtype.
OBJECTIVE
PGE2 has been shown to induce relaxations in precontracted human pulmonary venous preparations, while in pulmonary arteries this response was not observed. We investigated and characterized the prostanoid receptors which are activated by PGE2 in the human pulmonary veins.


METHODS
Human pulmonary arteries and veins were cut as rings and set up in organ baths in presence of a TP antagonist. A pharmacological study was performed using selective EP1-4 ligands. The cellular localization of the EP4 receptors by immunohistochemistry and their corresponding transcripts were also investigated in these vessels.


RESULTS
PGE2 and the EP4 agonists (L-902688, ONO-AE1-329) induced potent vasodilatation of the human pulmonary vein, pEC50 values: <7.22+/-0.20, 8.06+/-0.12 and 7.80+/-0.09, respectively. These relaxations were inhibited by the EP(4) antagonist GW627368X and not modified in presence of the DP antagonist L-877499. Higher concentrations (>or=1 microM) of the EP2 agonist ONO-AE1-259 induced relaxations of the veins. The EP4 agonists had no effect on the precontracted arteries. Finally, the EP(1) antagonists ONO-8713 and SC-51322 potentiated the relaxation of the veins induced by PGE2. EP4 and EP1 receptors were detected by immunohistochemistry in the veins but not in the arteries. EP4 mRNA accumulation was also greater in the veins when compared with the arterial preparations.


CONCLUSIONS
Of the 4 EP receptor subtypes, smooth muscle cells in the human pulmonary vein express the EP4 and EP1 receptor subtypes. The relaxations induced by PGE2 in this vessel result from the activation of the EP4 receptor.
INSERM U698, Paris, France.
N
N
Foudi
L
L
Kotelevets
L
L
Louedec
G
G
Leséche
D
D
Henin
E
E
Chastre
X
X
Norel
D000368:Aged; D015232:Dinoprostone / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism; D011651:Pulmonary Artery / Q000187:drug effects / Q000378:metabolism; D011667:Pulmonary Veins / Q000187:drug effects / Q000378:metabolism*; D018078:Receptors, Prostaglandin E / Q000187:drug effects* / Q000378:metabolism*; D058306:Receptors, Prostaglandin E, EP1 Subtype; D058309:Receptors, Prostaglandin E, EP4 Subtype; D014664:Vasodilation / Q000187:drug effects
C545635:PTGER1 protein, human; C545650:PTGER4 protein, human; D018078:Receptors, Prostaglandin E; D058306:Receptors, Prostaglandin E, EP1 Subtype; D058309:Receptors, Prostaglandin E, EP4 Subtype; D015232:Dinoprostone