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PMID: 7537754 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Autocrine inhibition of Na+/K(+)-ATPase by nitric oxide in mouse proximal tubule epithelial cells.

The Journal of clinical investigation ·Vol. 95 ·No. 5 ·1995-05-00 ·Pages 2083-8

Guzman NJ, Fang MZ, Tang SS, Ingelfinger JR, Garg LC

Abstract

An inducible nitric oxide synthase has recently been described in proximal tubule epithelium. To investigate the effects of proximal tubule NO on Na+/K(+)-ATPase, we induced NO production in mouse proximal tubule epithelial cells by treatment with lipopolysaccharide (LPS) and interferon-gamma (IFN gamma) followed by determinations of ouabain-sensitive ATPase activity. Na+/K(+)-ATPase activity decreased after 4 h of LPS/IFN gamma treatment, reaching maximal inhibition after 24 h (34% reduction in activity). The inhibition of Na+/K(+)-ATPase activity by LPS/IFN gamma was prevented by simultaneous incubation with N omega-nitro L-arginine and markedly blunted by removal of L-arginine from the medium. The NO donors sodium nitroprusside and SIN-1 also inhibited Na+/K(+)-ATPase activity to a similar extent than LPS/IFN gamma. However, treatment with 8-pCPT-cGMP only modestly reduced Na+/K(+)-ATPase activity. Interestingly, superoxide dismutase prevented the inhibitory effects of NO on Na+/K(+)-ATPase activity, suggesting a role for peroxynitrite in this inhibition. We conclude that NO generated by mouse proximal tubule epithelial cell iNOS inhibits Na/K ATPase activity in an autocrine fashion and that this inhibition is accompanied by a reduction in Na-dependent solute transport.

MeSH Terms
Amino Acid Oxidoreductases/biosynthesis Analysis of Variance Animals Arginine/analogs & derivatives,pharmacology Cells, Cultured Cyclic GMP/analogs & derivatives,pharmacology Enzyme Induction Epithelium/drug effects,enzymology Interferon-gamma/pharmacology Kidney Tubules, Proximal/enzymology Kinetics Lipopolysaccharides/pharmacology Mice Nitric Oxide/physiology Nitric Oxide Synthase Nitroarginine Nystatin/pharmacology Sodium-Potassium-Exchanging ATPase/antagonists & inhibitors Superoxide Dismutase/pharmacology Thionucleotides/pharmacology
Chemicals
Lipopolysaccharides Thionucleotides Nystatin Nitroarginine Nitric Oxide 8-((4-chlorophenyl)thio)cyclic-3',5'-GMP Interferon-gamma Arginine Nitric Oxide Synthase Superoxide Dismutase Amino Acid Oxidoreductases Sodium-Potassium-Exchanging ATPase Cyclic GMP
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Guzman N J
Department of Pharmacology, University of Florida College of Medicine, Gainesville, USA.
Fang M Z
Tang S S
Ingelfinger J R
Garg L C
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Article Info
Journal
The Journal of clinical investigation
Abbr.
J Clin Invest
ISSN
0021-9738
DOI
10.1172/JCI117895
Published
1995-05-00
Pages
2083-8
Language
English
Region
United States
NLM ID
7802877
PMCID
PMC295802
Subset
IM
Grants
NIAAA NIH HHS · AA-09888 · United States
NHLBI NIH HHS · HL-43131 · United States
NHLBI NIH HHS · HL-48455 · United States
External Links
PubMed source DOI: 10.1172/JCI117895 PMC Full Text View journal details
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