Inhibition of prostaglandin E2 synthesis by a blocker of epithelial chloride channels
Breuer, W.; Skorecki, K.L.
Biochemical and Biophysical Research Communications 163(1): 398-405
1989
ISSN/ISBN: 0006-291X PMID: 2549993 Document Number: 346156
Arginine-vasopressin (AVP) elicits a variety of responses in cultured cat mesangial cells, among them stimulation of prostanglandin biosynthesis and activation of Cl- channels. AVP produced an 11-fold increase over basal levels in prostanglandin E2 release from cultured mesangial cells. This response was completely inhibited by 25.mu.M indomethacin and 82 .+-. 5% inhibited by 25.mu.M 5-nitro-2-(3-phenylpropylamino)-benzoic acid (NPPB) which is a potent blocker of epithelial Cl- channels. The IC50 for NPPB inhibition of prostaglandin E2 release was 8.mu.M. Indomethacin and NPPB at 25.mu.M also inhibited AVP-stimulated ceullular accumulation of prostaglandin E2 by 98% and 79 .+-. 7% respectively. The inhibitory effect of NPPB was not due to interference with the cellular response to AVP since at 50.mu.M it did not block AVP-stimulated release of arachidonate metabolites from cells metabolically labeled with [3H] arachidonic acid. It is suggested that NPPB inhibition of prostaglandin E2 synthesis is at the cyclooxygenase level on the basis of its structural similarity to the fenamic acid type of cyclooxygenase inhibitors.