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Nitric oxide derived from L-arginine impairs cytoplasmic pH regulation by vacuolar-type H+ ATPases in peritoneal macrophages
The ability of macrophages (Mos) to function within an acidic environment has been shown to depend on cytoplasmic pH (pHi) regulation by vacuolar-type H+ ATPases. Mos metabolize L-arginine via an oxidative pathway that generates nitric oxide, nitrate, and nitrite. Since each of these products could...
Formato: | Texto |
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Lenguaje: | English |
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The Rockefeller University Press
1991
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2119012/ https://www.ncbi.nlm.nih.gov/pubmed/1658185 |
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collection | PubMed |
description | The ability of macrophages (Mos) to function within an acidic environment has been shown to depend on cytoplasmic pH (pHi) regulation by vacuolar-type H+ ATPases. Mos metabolize L-arginine via an oxidative pathway that generates nitric oxide, nitrate, and nitrite. Since each of these products could potentially inhibit vacuolar-type H+ ATPases, we investigated the effect of L-arginine metabolism on Mo pHi regulation in thioglycolate-elicited murine peritoneal Mos. H+ ATPase- mediated pHi recovery from an imposed cytoplasmic acid load was measured fluorometrically. When Mos were incubated with L-arginine (0.25-2.0 mM), their rate of pHi recovery declined progressively from 2 to 6 h of incubation. By contrast, the recovery rate of cells incubated in arginine-free medium remained stable over the same period. The impairment of pHi recovery was specific for L-arginine, and was blocked competitively by NG-monomethyl-L-arginine, demonstrating its dependence on L-arginine metabolism. In addition, the inhibition of pHi recovery was enhanced by lipopolysaccharide, an agent known to stimulate L- arginine metabolism by Mos. Scavenging the L-arginine metabolite nitric oxide with either ferrous sulphate or ferrous myoglobin prevented the inhibition of pHi recovery, implying that L-arginine-derived nitric oxide was the species responsible for the inhibition. This concept was supported by the finding of elevated nitrite levels in the supernatant of cells incubated in L-arginine. Furthermore, incubation of Mos with sodium nitroprusside mimicked the L-arginine-dependent inhibition of H+ ATPase activity. Treatment with the cyclic GMP analogue, 8- bromoguanosine 3':5'-cyclic monophosphate, similarly impaired Mo pHi recovery, suggesting that a nitric oxide-stimulated elevation of cyclic GMP may contribute to the L-arginine-dependent inhibition of pHi regulation. |
format | Text |
id | pubmed-2119012 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 1991 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-21190122008-04-17 Nitric oxide derived from L-arginine impairs cytoplasmic pH regulation by vacuolar-type H+ ATPases in peritoneal macrophages J Exp Med Articles The ability of macrophages (Mos) to function within an acidic environment has been shown to depend on cytoplasmic pH (pHi) regulation by vacuolar-type H+ ATPases. Mos metabolize L-arginine via an oxidative pathway that generates nitric oxide, nitrate, and nitrite. Since each of these products could potentially inhibit vacuolar-type H+ ATPases, we investigated the effect of L-arginine metabolism on Mo pHi regulation in thioglycolate-elicited murine peritoneal Mos. H+ ATPase- mediated pHi recovery from an imposed cytoplasmic acid load was measured fluorometrically. When Mos were incubated with L-arginine (0.25-2.0 mM), their rate of pHi recovery declined progressively from 2 to 6 h of incubation. By contrast, the recovery rate of cells incubated in arginine-free medium remained stable over the same period. The impairment of pHi recovery was specific for L-arginine, and was blocked competitively by NG-monomethyl-L-arginine, demonstrating its dependence on L-arginine metabolism. In addition, the inhibition of pHi recovery was enhanced by lipopolysaccharide, an agent known to stimulate L- arginine metabolism by Mos. Scavenging the L-arginine metabolite nitric oxide with either ferrous sulphate or ferrous myoglobin prevented the inhibition of pHi recovery, implying that L-arginine-derived nitric oxide was the species responsible for the inhibition. This concept was supported by the finding of elevated nitrite levels in the supernatant of cells incubated in L-arginine. Furthermore, incubation of Mos with sodium nitroprusside mimicked the L-arginine-dependent inhibition of H+ ATPase activity. Treatment with the cyclic GMP analogue, 8- bromoguanosine 3':5'-cyclic monophosphate, similarly impaired Mo pHi recovery, suggesting that a nitric oxide-stimulated elevation of cyclic GMP may contribute to the L-arginine-dependent inhibition of pHi regulation. The Rockefeller University Press 1991-11-01 /pmc/articles/PMC2119012/ /pubmed/1658185 Text en This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Articles Nitric oxide derived from L-arginine impairs cytoplasmic pH regulation by vacuolar-type H+ ATPases in peritoneal macrophages |
title | Nitric oxide derived from L-arginine impairs cytoplasmic pH regulation by vacuolar-type H+ ATPases in peritoneal macrophages |
title_full | Nitric oxide derived from L-arginine impairs cytoplasmic pH regulation by vacuolar-type H+ ATPases in peritoneal macrophages |
title_fullStr | Nitric oxide derived from L-arginine impairs cytoplasmic pH regulation by vacuolar-type H+ ATPases in peritoneal macrophages |
title_full_unstemmed | Nitric oxide derived from L-arginine impairs cytoplasmic pH regulation by vacuolar-type H+ ATPases in peritoneal macrophages |
title_short | Nitric oxide derived from L-arginine impairs cytoplasmic pH regulation by vacuolar-type H+ ATPases in peritoneal macrophages |
title_sort | nitric oxide derived from l-arginine impairs cytoplasmic ph regulation by vacuolar-type h+ atpases in peritoneal macrophages |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2119012/ https://www.ncbi.nlm.nih.gov/pubmed/1658185 |