Nigericin sodium

Calcium pumping into the endoplasmic reticulum (ER) lumen is thought to be coupled to a countertransport of protons through sarcoplasmic/endoplasmic reticulum calcium ATPase (SERCA) and the members of the ClC family of chloride channels. However, pH in the ER lumen remains neutral, which suggests a mechanism responsible for proton re-entry. We studied whether cation-proton exchangers could act as routes for such a re-entry. ER Ca(2+) uptake was measured in permeabilized immortalized hypothalamic neurons, primary rat cortical neurons and mouse cardiac fibers. Replacement of K(+) in the uptake solution with Na(+) or tetraethylammonium led to a strong inhibition of Ca(2+) uptake in neurons and cardiomyocytes. Furthermore, inhibitors of the potassium-proton exchanger (quinine or propranolol) but not of the sodium-proton exchanger reduced ER Ca(2+) uptake by 56-82%. Externally added nigericin, a potassium-proton exchanger, attenuated the inhibitory effect of propranolol.

Tryptophan metabolism through the kynurenine pathway leads to several neuroactive compounds, including kynurenic and picolinic acids. Xanthurenic acid (Xa) has been generally considered as a substance with no physiological role but possessing toxic and apoptotic properties. In the present work, we present several findings which support a physiological role for endogenous Xa in synaptic signalling in brain. This substance is present in micromolar amounts in most regions of the rat brain with a heterogeneous distribution. An active vesicular synaptic process inhibited by bafilomycin and nigericin accumulates xanthurenate into pre-synaptic terminals. A neuronal transport, partially dependant on adenosine 5'-triphosphate (ATP), sodium and chloride ions exists in NCB-20 neurons which could participate in the clearance of extracellular xanthurenate. Both transports (neuronal and vesicular) are greatly enhanced by the presence of micromolar amounts of zinc ions.

BACKGROUND: Cells within the acidic extracellular environment of solid tumours maintain their intracellular pH through the activity of the Na(+)/H(+) exchanger and the Na(+) dependent Cl(-)/HCO(3)(-) exchanger. The inhibition of these mechanisms could therefore inhibit cancer cell growth.

This study deals with the effects of the agents that dissipate the individual components of the proton motive force (short-chain fatty acids, nigericin, and valinomycin) upon the methyl viologen-coupled nitrate reductase activity in intact cells. Substitution of butyrate or acetate for chloride in Tris-buffered assay media resulted in a marked inhibition at pH 7. In a Tris--chloride buffer of neutral pH, the reaction was almost fully inhibitable by nigericin. Alkalinisation increased the IC(50) value for nigericin and decreased the maximal inhibition attained. Both types of inhibitions could be reversed by the permeabilisation of cells or by the addition of nitrite, and that caused by nigericin disappeared at high extracellular concentrations of potassium. These data indicate that nitrate transport step relies heavily on the pH gradient at neutral pH. Since the affinity of cells for nitrate was strongly diminished by imposing an inside-positive potassium (or lithium) diffusion potential at alkaline external pH, a potential dependent step may be of significance in the transporter cycle under these conditions.