Jy. Crider et al., Endogenous EP4 prostaglandin receptors coupled positively to adenylyl cyclase in Chinese hamster ovary cells: pharmacological characterization, PROS LEUK E, 62(1), 2000, pp. 21-26
Citations number
23
Categorie Soggetti
Cell & Developmental Biology
Journal title
PROSTAGLANDINS LEUKOTRIENES AND ESSENTIAL FATTY ACIDS
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.