Prostaglandins, Leukotrienes and Essential Fatty Acids (PLEFA) 2005-04-01

Investigation of the agonist activity of prostacyclin analogues on prostanoid EP4 receptors using GW 627368 and taprostene: evidence for species differences.

R L Jones, K M Chan

Index: Prostaglandins Leukot. Essent. Fatty Acids 72(4) , 289-99, (2005)

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Abstract

The possibility that the prostacyclin analogues AFP-07 and cicaprost relax saphenous vein preparations of pig, guinea-pig and rabbit by simultaneously activating prostanoid EP4 and IP (prostacyclin) receptors was investigated using the high-affinity EP4 antagonist GW 627368. The IP receptor system in each preparation was suppressed with the partial agonist taprostene. The results indicate that AFP-07 and cicaprost are moderately potent EP4 agonists on pig saphenous vein, but much weaker EP4 agonists on guinea-pig saphenous vein. GW 627368 did not antagonise AFP-07- and cicaprost-induced relaxation of rabbit saphenous vein, which contrasts with a previous study using the EP4 blocker AH 23848. However, treatment with taprostene was of less value due to poorer antagonism of the rabbit IP system; this may be related to the presence of a sensitive EP2 relaxant system. Relaxation of each preparation induced by the selective EP2 agonist ONO-AE1-259 was unaffected by GW 627368, with and without taprostene.