| First Author | Regan JW | Year | 1994 |
| Journal | Mol Pharmacol | Volume | 46 |
| Issue | 2 | Pages | 213-20 |
| PubMed ID | 8078484 | Mgi Jnum | J:32754 |
| Mgi Id | MGI:80244 | Citation | Regan JW, et al. (1994) Cloning of a novel human prostaglandin receptor with characteristics of the pharmacologically defined EP2 subtype. Mol Pharmacol 46(2):213-20 |
| abstractText | A cDNA that when expressed has the binding and functional characteristics of the pharmacologically defined EP2 prostaglandin (PG) receptor [Cardiovasc. Drug Rev. 11:165-179 (1993)] has been cloned from a human placenta library. This clone, known as Hup-4, encodes a protein of 358 amino acids that has only approximately 30% overall identity with other PG receptors, including mouse and human clones that have been designated as EP2 receptors [J. Biol. Chem. 268:7759-7762 (1993); Biochem. Biophys. Res. Commun. 197:263-270 (1993)]. In COS-7 cells transfected with Hup-4, PGE2 stimulated the formation of cAMP with an EC50 of approximately 50 nM. The EP2-selective agonists AH13205 and butaprost were also active, with EC50 values in the range of 2-6 microM. The order of potency of PGs for competition with binding of [3H]PGE2 to membranes prepared from COS-7 cells transfected with Hup-4 was PGE2 > or = PGE1 > 16,16-dimethyl-PGE2 > or = 11-deoxy-PGE1 > butaprost > AH13205 > 19(R)-OH-PGE2. Natural PGs and analogues that are selective for the FP (PGF2a), DP (PGD2), EP1 (sulprostone), EP3 (MB 28767), and EP4 (1-OH-PGE1) receptors were inactive or competed poorly with the binding of [3H]PGE2 (< 50% displacement of specific binding at 10 microM). Northern blot analysis showed the presence of a Hup-4 message of approximately 3.1 kilobases in mRNA from human lung and placenta. Reverse transcription-polymerase chain reaction studies also indicated that Hup-4 is probably expressed in human uterus and in HL-60 (human promyelocytic leukemia) cells. Our findings suggest that Hup-4 encodes the pharmacologically defined EP2 receptor, whereas the mouse and human cDNAs previously classified as EP2 may represent another EP receptor subtype or the recently defined EP4 subtype [Prostaglandins 47:151-168 (1994)]. |
