TEI-3356, a highly selective agonist for the prostaglandin EP3 receptor.
Recently, we cloned cDNAs for the three mouse PGE receptor subtypes, EP1, EP2 and EP3, and the prostacyclin receptor, and established cells that stably express each receptor. We examined the selectivity of TEI-3356, an isocarbacyclin analogue, compared with other EP agonists, sulprostone and misoprostol, using Chinese hamster ovary cells expressing each cloned receptor. TEI-3356 selectively displaced the [3H]PGE2 binding to EP3-expressing cell membranes, but showed very low affinity for both EP1 and EP2. Although TEI-3356 is an isocarbacyclin analogue, it showed low affinity for the prostacyclin receptor. On the other hand, sulprostone strongly displaced the [3H]PGE2 binding to EP1 and EP3, but not to EP2. Misoprostol weakly bound to the three subtypes without selectivity. TEI-3356 decreased the forskolin-induced cAMP formation in a concentration-dependent manner in the EP3-expressing cells, the half-maximal concentration for the inhibition being similar to that of sulprostone but lower than that of PGE2. These results demonstrate that TEI-3356 is a potent and highly selective agonist for the EP3 receptor.
Department of Physiological Chemistry, Faculty of Pharmaceutical Sciences, Kyoto University, Japan.
M
M
Negishi
A
A
Harazono
Y
Y
Sugimoto
A
A
Hazato
S
S
Kurozumi
A
A
Ichikawa
D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D000242:Cyclic AMP / Q000378:metabolism; D015232:Dinoprostone / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D011464:Epoprostenol / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D051379:Mice; D016595:Misoprostol / Q000378:metabolism / Q000494:pharmacology; D015394:Molecular Structure; D018078:Receptors, Prostaglandin E / Q000819:agonists* / Q000235:genetics / Q000378:metabolism
D018078:Receptors, Prostaglandin E; D016595:Misoprostol; C074591:TEI 3356; C016767:sulprostone; D011464:Epoprostenol; D000242:Cyclic AMP; D015232:Dinoprostone