Effect of prostaglandins on cyclic AMP production in cultured human ciliary muscle cells.
Prostaglandins (PGs) lower intraocular pressure by increasing uveoscleral outflow, presumably via a receptor-mediated mechanism coupled to a second messenger pathway in the ciliary muscle. In the present study, we examined the effect of prostanoids on cyclic AMP production in cultured human ciliary muscle cells. Cells were identified based on their expression of smooth muscle specific alpha-actin and monoclonal antibody against desmin. Cyclic AMP production in confluent cells incubated with buffer solution containing various concentrations of prostanoids was analyzed by radioimmunoassay. PGE2 caused a time-dependent increase in cyclic AMP concentrations which reached a maximum after 10 mins. With the exception of PGD2, all prostanoids produced a concentration-dependent increase in cyclic AMP levels with the following rank order of activity: PGE2 > 11-deoxy-PGE1 > 16,16-dimethyl PGE2 > sulprostone > PGF2alpha. PGE2-induced increase on cyclic AMP levels was unaffected by AH6809, an antagonist at both PGD2 (DP) and E2 (EP1) receptors. Flurbiprofen decreased basal cyclic AMP concentrations suggesting that intramurally-generated PGs stimulate the formation of the nucleotide in ciliary smooth muscle cells. PGE2-induced increases in cyclic AMP production was synergistic with those induced by the diterpene activator of adenylyl cyclase, forskolin. We conclude that prostanoids active at EP2-receptors can stimulate cyclic AMP production in cultured human ciliary muscle cells.
Zhan
G L
GL
Department of Opthalmology, University of Nebraska Medical Center, Omaha, USA.
Camras
C B
CB
Opere
C
C
Tang
L
L
Ohia
S E
SE
D000328:Adult; D002478:Cells, Cultured; D002924:Ciliary Body / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D000242:Cyclic AMP / Q000096:biosynthesis*; D015237:Dinoprost / Q000494:pharmacology; D015232:Dinoprostone / Q000494:pharmacology; D006801:Humans; D008297:Male; D011453:Prostaglandins / Q000494:pharmacology*
D011453:Prostaglandins; D015237:Dinoprost; D000242:Cyclic AMP; D015232:Dinoprostone