Characterization of chimeric prostacyclin/prostaglandin D(2) receptors.

The functional activity of two chimeric mouse prostacyclin/prostaglandin D(2) (IP/DP) receptors, in which the carboxyl-terminal region of the IP receptor was progressively replaced by that of the DP receptor, was examined in Chinese hamster ovary (CHO) cells. The order of potency of prostaglandin D(2), prostaglandin E(2) and the IP receptor agonists cicaprost, iloprost and BMY 45778 (3-[4-(4, 5-diphenyl-2-oxazolyl)-5-oxazolyl]phenoxy]acetic acid) to stimulate cyclic AMP production was identical for the IP(N-VII)/DP(C), IP(N-V)/DP(VI-C) and wild-type IP receptors. IP(N-VII)/DP(C) receptor-expressing cells showed increases in basal adenylate cyclase activity, agonist potency and coupling efficiency. In addition, the intrinsic activity of the partial IP receptor agonists BMY 45778 and PGE(2) was significantly increased in IP(N-VII)/DP(C) receptor-expressing cells. Therefore, substitution of just the carboxyl-terminal tail of the IP receptor by that of the DP receptor appears to result in a chimeric IP/DP receptor with all the properties of a constitutively-active receptor.