1. European Journal of Cell Biology, 84 Suppl.55 (2005 March) - C Elsevier GmbH. Jena


The osmotically active "proton"-substitute
alkali metal lithium in medication and therapy

RKI-Institute, Saliterweg 1, D-9343 7 Furth im Wald,

Li has a myriad of effects on cell Transport mechanisms, second messenger pathways, and neurotransmitter dynamics. The two major involved neurotransmitters in the pathogenesis of affective disorders are 5HT and NE, which are modulated by Li. Li disturbes hydrogen bridges and the electric conductivity, slows down oscillations involved in memory and thinking, in ther-moregulation.

Li decreases at clinically relevant therapeutic range noradrenergic transmission, NE release, inhibits basal and beta adrenoceptor-dependent adenylate cyclase, is modulating the phosphatidylinositol pathway. Li is an ion that substitutes for sodium and/or protons: Li distributes rapidly to liver and kidney, Li enters cells via sodium channels, incl. K(Na)/H20-pump (FOF1-ATPase): extruded by the active cation pump (and K,Na/H-exchange-system) at about one-tenth of the rate of sodium: Li accumulates therefore in cells.

At therapeutic plasma levels the side effects of Li includes fatique (liver counts). Above 2 mEq/L more severe toxic signs may occur. The toxicity of Li is increased by factors that deplete the body of sodium. Restriction of dietary sodium dramatically increases the renal reabsorption of Li and can lead to severe toxicity. Similarly, diuretics that lead to sodium loss may augment Li toxicity: kidney damage (cysts), chronic allergic reactions (elevated IgE).

Ref.at www.rki-i.com, weiteres folgt...
Email: kiehl@rki-i.com

Jahrestagung der Deutschen Gesellschaft für Zellbiologie


Evidence for mitochondrial 2,4-dinitrophenol accumulation across the Pi/H+ symport system

Reinhold Kiehl
RKI-Institute, Saliterweg 1, D-9343 7 Furth im Wald,
www.rki-i.com, www.dr-kiehl.net

Abbreviations:NSPM, N\'-[N\'\'-n-nonyl-4sulfamoylphenyl]-maleimide, NEM, N-ethylmaleimide; DNP, 2,4-dinitrophenol, NPA, 2-azido-4-nitrophenol

Summary: N\'-[N\'\'-n-nonyl-4-sulfamoylphenyl]maleimide (NSPM) has been shown to be a very potent and specific reagent for inhibition or stimulation of various mitochondrial membrane-associated functions: ß-hydroxybutyrate-dehydrogenase, ATP/ADP-carrier, calcium- and potassium transport. 20 nmol NSPM/mg mitochondria inhibit the phosphate(H+) activated Pi/H+symport system, prevent uncoupling by the classical uncoupler 2,4-dinitrophenol (DNP), and compete with the DNP analog compound 2-azido-4-nitrophenol (NPA). Furthermore, in this investigation we found that 20 nmol NSPM/mg mitochondria prevent DNP (H+)activated DNP accumulation. lt is concluded that DNP uncouples these mitochondria only after being transported into mitochondria by the Pi/H+-symport system. A further conclusion is that NSPM reacts at the phosphate binding site, thereby abolishing Pi/DNP-binding and Transport.

Key words: Thiol-reagent, Pi/H+-symport, uncoupling, 2,4-dinitrophenol binding, 2,4-dinitrophenol-accumulation.

References: Kiehl, R., Internet-files at www.rki-i.com, www.dr-kiehl.net (free pdf- or html-files, book-chapters under publications, materials)

Email: kiehl@rki-i.com

Jahrestagung der Deutschen Gesellschaft für Zellbiologie

...weiteres unter Materialien, Buch-Kapitel...