Alkaline pH, membrane potential, and magnesium cations are negative modulators of purine nucleotide inhibition of H+ and Cl- transport through the uncoupling protein of brown adipose tissue mitochondria
Jazyk angličtina Země Spojené státy americké Médium print
Typ dokumentu časopisecké články
PubMed
2463983
DOI
10.1007/bf00768922
Knihovny.cz E-zdroje
- MeSH
- chloridy metabolismus MeSH
- hnědá tuková tkáň účinky léků metabolismus MeSH
- hořčík farmakologie MeSH
- iontové kanály účinky léků metabolismus MeSH
- koncentrace vodíkových iontů MeSH
- křečci praví MeSH
- křeček rodu Mesocricetus MeSH
- membránové potenciály MeSH
- membránové proteiny metabolismus MeSH
- mitochondriální proteiny MeSH
- mitochondrie metabolismus MeSH
- palmitoylkoenzym A farmakologie MeSH
- purinové nukleotidy farmakologie MeSH
- techniky in vitro MeSH
- transportní proteiny * MeSH
- uncoupling protein 1 MeSH
- valinomycin farmakologie MeSH
- zvířata MeSH
- Check Tag
- křečci praví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- chloridy MeSH
- hořčík MeSH
- iontové kanály MeSH
- membránové proteiny MeSH
- mitochondriální proteiny MeSH
- palmitoylkoenzym A MeSH
- purinové nukleotidy MeSH
- transportní proteiny * MeSH
- uncoupling protein 1 MeSH
- valinomycin MeSH
Modulators of purine nucleotide (PN) inhibition of H+ and Cl- transport mediated by the uncoupling protein (UP) of brown adipose tissue (BAT) mitochondria were studied: Alkalinization strongly diminishes GDP inhibition of H+ transport (delta log IC50 = -delta pHout), while more intensive inhibition of Cl- transport is only slightly altered. Higher delta psi decreases GDP inhibition of H+ transport. Mg2+, but not palmitoyl-CoA, decreases PN inhibitory ability. Simulations of conditions similar to those found in BAT cells in the resting state and in the thermogenic state showed that three factors act in concert: pH, Mg2+, and free fatty acids (FFA): (a) with endogenous FFA present and 2 mM ATP and 0.5 mM AMP (pH 7.1), H+ transport was inhibited by 95% in the absence of Mg2+, while by 60% with Mg2+; (b) 0.5 mM ATP and 1 mM AMP, H+ transport was inhibited by 40% without Mg2+ and by 30% with Mg2+. State b thus represents a model thermogenic state, while state a represents a resting state. However, the latter state in vivo must be accomplished either by combustion or FFA or by elimination of Mg2+ to attain a total inhibition of H+ transport (cf. a). The model of UP possessing two independent channels, an H+ channel and a Cl- channel, controlled from a single PN-binding site is supported by independent kinetics by different pH dependence of H+ and Cl- transport, and by a lower sensitivity of H+ transport to PN inhibition.
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Mitochondrial Uncoupling Proteins: Subtle Regulators of Cellular Redox Signaling