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

Prostaglandins Leukot Essent Fatty Acids. 2005 Apr;72(4):289-99. doi: 10.1016/j.plefa.2004.12.002.

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.

MeSH terms

  • Animals
  • Dinoprostone / analogs & derivatives*
  • Dinoprostone / pharmacology
  • Epoprostenol / analogs & derivatives*
  • Epoprostenol / pharmacology*
  • Guinea Pigs
  • Male
  • Rabbits
  • Receptors, Prostaglandin E / agonists*
  • Receptors, Prostaglandin E / metabolism
  • Receptors, Prostaglandin E, EP4 Subtype
  • Saphenous Vein / drug effects
  • Species Specificity
  • Swine

Substances

  • 9-deoxy-9-chloro-15-deoxy-16-hydroxy-17,17-trimethylene-19,20-didehydroprostaglandin E2
  • AFP 07
  • Receptors, Prostaglandin E
  • Receptors, Prostaglandin E, EP4 Subtype
  • taprostene
  • Epoprostenol
  • Dinoprostone