Endogenous EP4 prostaglandin receptors coupled positively to adenylyl cyclase in Chinese hamster ovary cells: pharmacological characterization

The purpose of these studies was to investigate the pharmacology of E-serie s and selected prostaglandins of other classes on adenylyl cyclase activity in Chinese hamster ovary (CHO) cells expressing an endogenous prostanoid r eceptor and to compare these responses with those from immortalized human n onpigmented ciliary epithelial (NPE) cells containing the EP2 receptor. 11- deoxy-PGE(2) was the most potent of the 16 prostanoid agonists tested for s timulating cAMP formation with a potency (EC50) value of 26 +/- 6 nM in the CHO cells. The endogenous ligand, PGE(2), exhibited potencies of 40 +/- 7 nM (n = 24) in the CHO cells and 67 +/- 9 nM (n = 46) in the NPE cells. The EP2 receptor agonist, butaprost, produced an EC50 value of 212 +/- 58 nM ( n = 4) in the NPE cells while being inactive (EC50 > 10 000 nM, n = 6) in t he CHO cells. The EP2 receptor selective antagonists, AH22921 and AH23848B, at a concentration of 30 mu M, caused a 2.2 +/- 0.5 (n = 4) and 8.2 +/- 2. 7 (n = 4) fold rightward shift in the PGE(2) concentration-response curves in the CHO cells, yielding apparent pK(b) values of 4.6 +/- 0.6 and 5.3 +/- 0.2 (n = 4), respectively. AH22921 and AH23848B were non-competitive antag onists at the CHO cell EP2 receptor, but did not shift the PGE(2) concentra tion-response curves in the NPE cells containing the EP2 receptor. These st udies have characterized the functional prostaglandin receptors in CHO cell s pharmacologically and shown them to be consistent with the EP4 subtype. ( C) 2000 harcourt Publishers Ltd.