Extracellular cyclic gmp inhibits transepithelial sodium transport
by llcpk1 renal tubular cells.
Chevalier, Robert L., Guodong D. Fang, Marjorie Garmey.
Department of Pediatrics, University of Virginia, Charlottesville,
Virginia
APStracts 2:0152F, 1995.
Both atrial natriuretic peptide (ANP) and sodium nitroprusside (SNP)
inhibit tubular sodium reabsorption by generation of cyclic GMP
(cGMP). To determine the role of extracellular cGMP in this response,
monolayers of porcine renal tubular LLCPK1 cells were incubated for 5
min with ANP, SNP, cGMP, or 8-bromo-cGMP (10 nM to 0.1 mM).
Transepithelial sodium transport was measured as amiloride
-inhibitable short-circuit current (Isc). Incubation of cell
monolayers with 1 [mu]M of ANP, cGMP, or 8-bromo-cGMP inhibited Isc
by over 70%, as did SNP at 100 [mu]M (p<0.01). Cyclic AMP (0.1
mM) had no significant effect. Incubation of monolayers with 1 [mu]M
LY83583 (an inhibitor of guanylyl cyclase), 10 [mu]M probenecid (an
organic anion transport inhibitor), or pre-incubation with 1 [mu]g/ml
nocodazole (a microtubule disrupter) reduced extracellular
accumulation of cGMP (p<0.05) and abolished the SNP-mediated
reduction of Isc. However, addition of these inhibitors did not
affect reduction of Isc by exogenous cGMP. We conclude that SNP
inhibits sodium transport by LLCPK1 monolayers through generation of
cGMP, but that extrusion of cGMP out the cell is necessary for its
effect.
Received 14 June 1995; accepted in final form 15 August 1995.
APS Manuscript Number F192-5.
Article publication pending Am. J. Physiol. (Renal Fluid Electrolyte
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 23 September 1995.