Ligand binding specificities of the eight types and subtypes of the mouse prostanoid receptors expressed in Chinese hamster ovary cells

1 Eight types and subtypes of the mouse prostanoid receptor, the prostaglandin D (DP) receptor, the prostaglandin F (FP) receptor, the prostaglandin I (IP) receptor, the thromboxane A (TP) receptor and the EP 1 , EP 2 , EP 3 and EP 4 subtypes of the prostaglandin E receptor, were stably expressed in Chinese hamster ovary cells. Their ligand binding characteristics were examined with thirty two prostanoids and their analogues by determining the K i values from the displacement curves of radioligand binding to the respective receptors. 2 The DP, IP and TP receptors showed high ligand binding specificity and only bound their own putative ligands with high affinity such as PGD 2 , BW245C and BW868C for DP, cicaprost, iloprost and isocabacyclin for IP, and S‐145, I‐BOP and GR 32191 for TP. 3 The FP receptor bound PGF 2α and fluprostenol with K i values of 3–4 n M . In addition, PGD 2 , 17‐phenyl‐PGE 2 , STA 2 , I‐BOP, PGE 2 and M&B̀‐28767 bound to this receptor with K i values less than 100 n M . 4 The EP 1 receptor bound 17‐phenyl‐PGE 2 , sulprostone and iloprost in addition to PGE 2 and PGE 1 , with K i values of 14–36 n M . 16,16‐dimethyl‐PGE 2 and two putative EP 1 antagonists, AH6809 and SC‐19220, did not show any significant binding to this receptor. M&B‐28767, a putative EP 3 agonist, and misoprostol, a putative EP 2 /EP 3 agonist, also bound to this receptor with K i values of 120 n M . 5 The EP 2 and EP 4 receptors showed similar binding profiles. They bound 16,16‐dimethyl PGE 2 and 11‐deoxy‐PGE 1 in addition to PGE 2 and PGE 1 . The two receptors were discriminated by butaprost, AH‐13205 and AH‐6809 that bound to the EP 2 receptor but not to the EP 4 receptor, and by 1‐OH‐PGE 1 that bound to the EP 4 but not to the EP 2 receptor. 6 The EP 3 receptor showed the broadest binding profile, and bound sulprostone, M&B‐28767, GR63799X, 11‐deoxy‐PGE 1 , 16,16‐dimethyl‐PGE 2 and 17‐phenyl‐PGE 2 , in addition to PGE 2 and PGE 1 , with K i values of 0.6–3.7 n M . In addition, three IP ligands, iloprost, carbacyclin and isocarbacyclin, and one TP ligand, STA 2 , bound to this receptor with K i values comparable to the K i values of these compounds for the IP and TP receptors, respectively. 7 8‐Epi‐PGF 2α showed only weak binding to the IP, TP, FP, EP 2 and EP 3 receptor at 10 μ M concentration.British Journal of Pharmacology (1997) 122 , 217–224; doi: 10.1038/sj.bjp.0701367