Investigation of the agonist activity of prostacyclin analogues on prostanoid EP4 receptors using GW 627368 and taprostene: evidence for species differences.
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.
Jones
R L
RL
Department of Pharmacology, Faculty of Medicine, Chinese University of Hong Kong, Hong Kong SAR, China. robert.l.jones@strath.ac.uk
Chan
K M
KM
D000818:Animals; D015232:Dinoprostone / Q000031:analogs & derivatives* / Q000494:pharmacology; D011464:Epoprostenol / Q000031:analogs & derivatives* / Q000494:pharmacology*; D006168:Guinea Pigs; D008297:Male; D011817:Rabbits; D018078:Receptors, Prostaglandin E / Q000819:agonists* / Q000378:metabolism; D058309:Receptors, Prostaglandin E, EP4 Subtype; D012501:Saphenous Vein / Q000187:drug effects; D013045:Species Specificity; D013552:Swine
C499423:9-deoxy-9-chloro-15-deoxy-16-hydroxy-17,17-trimethylene-19,20-didehydroprostaglandin E2; C106191:AFP 07; D018078:Receptors, Prostaglandin E; D058309:Receptors, Prostaglandin E, EP4 Subtype; C039188:taprostene; D011464:Epoprostenol; D015232:Dinoprostone