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Vasorelaxation induced by prostaglandin E 2 in human pulmonary vein: role of the EP 4 receptor subtype
Author(s) -
Foudi N,
Kotelevets L,
Louedec L,
Leséche G,
Henin D,
Chastre E,
Norel X
Publication year - 2008
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/bjp.2008.214
Subject(s) - receptor , agonist , vasodilation , antagonist , receptor antagonist , prostaglandin , immunohistochemistry , endocrinology , medicine , prostanoid , blood vessel , vascular smooth muscle , vein , smooth muscle , chemistry
Background and purpose: PGE 2 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 PGE 2 in the human pulmonary veins. Experimental approach: 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 EP 1−4 ligands. The cellular localization of the EP 4 receptors by immunohistochemistry and their corresponding transcripts were also investigated in these vessels. Key results: PGE 2 and the EP 4 agonists (L‐902688, ONO‐AE1‐329) induced potent vasodilatation of the human pulmonary vein, pEC 50 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 (1 μ M ) of the EP 2 agonist ONO‐AE1‐259 induced relaxations of the veins. The EP 4 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 PGE 2 . EP 4 and EP 1 receptors were detected by immunohistochemistry in the veins but not in the arteries. EP 4 mRNA accumulation was also greater in the veins when compared with the arterial preparations. Conclusions and implications: Of the 4 EP receptor subtypes, smooth muscle cells in the human pulmonary vein express the EP 4 and EP 1 receptor subtypes. The relaxations induced by PGE 2 in this vessel result from the activation of the EP 4 receptor. British Journal of Pharmacology (2008) 154 , 1631–1639; doi: 10.1038/bjp.2008.214 ; published online 2 June 2008