IRREVERSIBLE ZINC ION INHIBITION OF (Na+‐K+)‐ADENOSINETRIPHOSPHATASE, Na+‐PHOSPHORYLATION, AND K + ‐p‐NITROPHENYLPHOSPHATASE OF ELECTROPHORUS ELECTRICUS ELECTROPLAX1

Gettelfinger, Dennis M.; Siegel, George J.

doi:10.1111/j.1471-4159.1978.tb06247.x

Cited by 11 publications

(3 citation statements)

References 18 publications

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“…Although further studies will be needed to establish the precise mechanisms by which zinc exposure leads to phosphorylation of Src tyrosine 220 and consequent kinase activation, it is attractive to postulate that this activation is mediated by zinc's known ability to inhibit the Na ϩ ͞K ϩ ATPase at micromolar concentrations (64)(65)(66), because the pharmacological inhibitor, ouabain, activates Src in cardiac myocytes (67,68 (67,68).…”

Section: Discussionmentioning

confidence: 99%

Zinc induces a Src family kinase-mediated up-regulation of NMDA receptor activity and excitotoxicity

Manzerra

Behrens

Canzoniero

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

106

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Zinc is coreleased with glutamate from excitatory nerve terminals throughout the central nervous system and acutely inhibits Nmethyl-D-aspartate (NMDA) receptor activation. Here we report that cultured murine cortical neurons briefly exposed to sublethal concentrations of zinc developed increased intracellular free Na ؉ , phosphorylation of Src kinase at tyrosine 220, and tyrosine phosphorylation of NMDA receptor 2A͞2B subunits, in a fashion sensitive to the Src family kinase inhibitor 4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine, PP2. Functionally, this zinc exposure produced a delayed increase in NMDA receptor current in perforated patch but not conventional whole-cell recordings, as well as an increase in NMDA receptor-mediated cell death. These observations suggest that the effect of synaptically released zinc on neuronal NMDA receptors may be biphasic: acute block, followed by Src family kinase-mediated up-regulation of NMDA receptor activity and cytotoxicity.

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Section: Discussionmentioning

confidence: 99%

Zinc induces a Src family kinase-mediated up-regulation of NMDA receptor activity and excitotoxicity

Manzerra

Behrens

Canzoniero

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

106

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“…Zinc-containing drugs have been shown in some, but not all, studies to reduce the duration of acute cough associated with viral upper respiratory infections [21][22][23][24][25]41,42 . The effect may be related to blockade of acid-sensing ion channels 18,43 , blockade of voltage gated ion channels 17 , modulation of NMDA-type glutamate receptor channels 44 that may also be relevant to cough suppression 13 , or neuronal sodium pump inhibition [16][17][18] . Drugs known to interact with sodium pumps dose-dependently suppress cough in guinea pigs and in patients 15,45,46 .…”

Section: Discussionmentioning

confidence: 99%

“…Selective neuronal sodium pump inhibitors therefore offer a potential therapeutic avenue for management of chronic cough. Zinc and other electrophilic metals inhibit Na+-K+ ATPase with some selectivity for neuronal isoforms [16][17][18] . Zinc is also an anti-oxidant that prevents mucus secretion in the airways and inhibits inflammation 19 .…”

Section: Introductionmentioning

confidence: 99%

Efficacy and tolerability of zinc acetate for treatment of chronic refractory cough: pilot randomised futility trial

Balasubramanian

Holbrook²,

Canning³

et al. 2023

ERJ Open Res

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BackgroundCough is the most reported symptom in the US, with chronic refractory cough representing significant morbidity to patients. Zinc acetate may have beneficial effects in the cough reflex pathway.Research QuestionWe sought to assess the safety and efficacy of zinc acetate in the management of chronic refractory cough.Study Design and MethodsThis was a randomized, placebo-controlled, parallel design pilot trial of individuals with chronic refractory cough. The effects of six weeks of zinc acetateversusplacebo on quality of life and symptoms as measured by the Cough Quality of Life Questionnaire (CQLQ), Leicester Cough Questionnaire (LCQ), Cough Visual Analog Score (C-VAS), and Global Assessment of Change in Cough (GACC) scores were evaluated. A futility analysis plan with a one-sided 80% confidence interval was used to compare treatment effect to published minimum clinically important differences (MCID) for each outcome.ResultsA total of 34 participants, 17 in each group, were enrolled and randomized. Participants were primarily White females with moderate-severe cough. Participants assigned to zinc acetate had a significant increase in serum zinc levels after 6 weeks while those assigned to placebo did not. Both groups showed improvement in CQLQ, LCQ, C-VAS, and GACC scores, but the treatment effects of zinc acetateversusplacebo were small with confidence intervals that did not include the MCIDs.InterpretationWe observed no benefit of zinc therapy over placebo on cough symptoms or quality of life and conclude that larger trials of zinc for chronic cough are not warranted.

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Inhibition of adenosine triphosphatases by gold

Nechay

1980

Arthritis & Rheumatism

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Inhibition of adenosine triphosphatase (ATPase) by chlorauric acid (Au3+) and gold sodium thiomalate (Au+) was studied in dog brain and kidney and in human kidney enzyme preparations. Au3+ indiscriminately affected ouabain‐sensitive (Na+ + K+‐dependent) ATPase and ouabain‐insensitive (Mg2+‐dependent) ATPase with concentrations for 50% inhibition (I50) approximately 10‐6 M. The I50 of Au3+ for Na+ + K+ ATPase was several‐fold higher in homogenates than in microsomal fractions. The enzyme was protected by bovine serum albumin. Although Au3+ and Au+ were equipotent against Mg2+ ATPase, Au+ inhibited Na+ + K+ ATPase 2 to 3 times more effectively than did Au3+. The inhibitory action of Au3+ (but not Au+) was potentiated by ascorbic acid, suggesting reduction of Au3+ to Au+ by ascorbic acid. The fractional inhibition of Na+ + K+ ATPase by Au3+ or Au+ was not affected by changing concentrations of NaCl, KCl, MgCl2, ATP, and MgATP. Decreasing pH from 8.0 to 6.8 enhanced both Au+ and Au3+ inhibition. We conclude that gold is one of the most potent nonspecific of Na+ + K+ ATPase, with characteristics differing from other metallic inhibitors of this enzyme system.

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IRREVERSIBLE ZINC ION INHIBITION OF (Na⁺‐K⁺)‐ADENOSINETRIPHOSPHATASE, Na⁺‐PHOSPHORYLATION, AND K ⁺ ‐p‐NITROPHENYLPHOSPHATASE OF ELECTROPHORUS ELECTRICUS ELECTROPLAX¹

Cited by 11 publications

References 18 publications

Zinc induces a Src family kinase-mediated up-regulation of NMDA receptor activity and excitotoxicity

Zinc induces a Src family kinase-mediated up-regulation of NMDA receptor activity and excitotoxicity

Efficacy and tolerability of zinc acetate for treatment of chronic refractory cough: pilot randomised futility trial

Inhibition of adenosine triphosphatases by gold

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