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
Language English Country United States Media print
Document type Journal Article
PubMed
2463983
DOI
10.1007/bf00768922
Knihovny.cz E-resources
- MeSH
- Chlorides metabolism MeSH
- Adipose Tissue, Brown drug effects metabolism MeSH
- Magnesium pharmacology MeSH
- Ion Channels drug effects metabolism MeSH
- Hydrogen-Ion Concentration MeSH
- Cricetinae MeSH
- Mesocricetus MeSH
- Membrane Potentials MeSH
- Membrane Proteins metabolism MeSH
- Mitochondrial Proteins MeSH
- Mitochondria metabolism MeSH
- Palmitoyl Coenzyme A pharmacology MeSH
- Purine Nucleotides pharmacology MeSH
- In Vitro Techniques MeSH
- Carrier Proteins * MeSH
- Uncoupling Protein 1 MeSH
- Valinomycin pharmacology MeSH
- Animals MeSH
- Check Tag
- Cricetinae MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Chlorides MeSH
- Magnesium MeSH
- Ion Channels MeSH
- Membrane Proteins MeSH
- Mitochondrial Proteins MeSH
- Palmitoyl Coenzyme A MeSH
- Purine Nucleotides MeSH
- Carrier Proteins * 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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Biochemistry. 1982 Mar 2;21(5):1082-9 PubMed
FEBS Lett. 1981 Aug 17;131(1):7-10 PubMed
Biochem Biophys Res Commun. 1985 Mar 15;127(2):509-16 PubMed
J Biol Chem. 1986 Jan 5;261(1):298-305 PubMed
Biochim Biophys Acta. 1984 Sep 27;766(3):679-84 PubMed
Physiol Rev. 1984 Jan;64(1):1-64 PubMed
Biochem Soc Trans. 1984 Jun;12 (3):388-90 PubMed
Essays Biochem. 1985;20:110-64 PubMed
Biochim Biophys Acta. 1979 Jul 3;549(1):1-29 PubMed
Eur J Biochem. 1983 Dec 1;137(1-2):197-203 PubMed
FEBS Lett. 1982 Nov 29;149(2):249-52 PubMed
Eur J Biochem. 1982 Dec 15;129(2):373-80 PubMed
Eur J Biochem. 1974 Dec 2;49(3):573-83 PubMed
FEBS Lett. 1984 May 7;170(1):186-90 PubMed
Experientia Suppl. 1978;32:25-32 PubMed
J Membr Biol. 1984;82(1):105-12 PubMed
Biochemistry. 1984 Apr 10;23(8):1640-5 PubMed
Biochim Biophys Acta. 1984 Jul 6;794(2):225-33 PubMed
Biochem Soc Trans. 1984 Jun;12 (3):390-3 PubMed
Eur J Biochem. 1987 May 4;164(3):687-94 PubMed
Biochim Biophys Acta. 1984 Dec 17;768(3-4):257-92 PubMed
Eur J Biochem. 1977 Jul 15;77(2):349-56 PubMed
Am J Physiol. 1985 Jun;248(6 Pt 1):E699-705 PubMed
Eur J Biochem. 1973 Sep 3;37(3):523-30 PubMed
FEBS Lett. 1977 Feb 15;74(1):43-6 PubMed
FEBS Lett. 1987 Jan 19;211(1):89-93 PubMed
EMBO J. 1985 Dec 1;4(12):3087-92 PubMed
Eur J Biochem. 1969 Nov;11(1):183-92 PubMed
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