Nonsteroidal antiinflammatory drugs modulate cl conductance and
fluid transport in bovine pigment epithelium.
Bialek, Steven, Judy Quong, Kefu Yu, and Sheldon S. Miller.
University of California, School of Optometry and Division of Cell
and Development, and Department of Molecular and Cell Biology.
Berkeley, California 94720
APStracts 2:0361C, 1995.
Nonsteroidal antiinflammatory drugs (NSAIDs) were added to the
solutions bathing the apical membrane of bovine retinal pigment
epithelium (RPE)?-?choroid explants. For example, niflumic acid (100
[mu]M) depolarized the basolateral membrane voltage (VB) by ?12 mV,
increased transepithelial potential (TEP) by 4.5 mV, decreased
intracellular Cl activity () by 13 mM, decreased transepithelial
resistance (Rt) by 17 ?cm2, and increased the membrane resistance
ratio (RA/RB) nearly three-fold. All of these changes are consistent
with an increase in basolateral membrane Cl conductance (). In
addition, niflumic acid caused intracellular [Ca2-]i to decrease by
16 nM and fluid transport rate to increase by 1.5 l x cm-2 x hr-1.
Flufenamic acid, structurally very similar to niflumic acid, had the
opposite effects on membrane voltage and resistance. Basal
application of the Cl channel blocker DIDS (4,4'-diisothiocyanato-
stilbene-2,2'-disulfonic acid) or current clamping VB to the reversal
potential for Cl (ECl) practically abolished the niflumic acid
response. The niflumic acid response was unaffected by protein kinase
inhibitors. These results suggest that certain NSAIDs can directly
alter Cl conductance in the bovine RPE, apparently independent of
cyclooxygenase inhibition.
Received 2 August 1995; accepted in final form 6 October 1995.
APS Manuscript Number C476-5.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 6 November 95