4-acetamido-4--isothiocyanatostilbene-2-2--disulfonic-acid and lanthanum-chloride

Sodium orthovanadate produced a dose-dependent release of histamine and prostaglandin D2 from rat peritoneal mast cells. The release of histamine was selectively inhibited by the anion channel blockers SITS and DIDS, and by theophylline and dibutyryl cyclic-AMP, but was unaffected by disodium cromoglycate and lanthanum ions. Unlike IgE-directed ligands, vanadate did not produce any change in the intracellular concentration of cyclic-AMP but did promote a substantial uptake of calcium-45 from the incubation medium. This effect paralleled the release of histamine. These results are discussed in terms of the possible mode of action of vanadate.

Topics: 4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid; 4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; Animals; Anions; Calcium; Cyclic AMP; Depression, Chemical; Female; Histamine Release; Ion Channels; Lanthanum; Male; Mast Cells; Ouabain; Peritoneal Cavity; Prostaglandin D2; Rats; Rats, Sprague-Dawley; Theophylline; Vanadates

The biochemical and Ca2+ transport pathways involved in generating the hormone-evoked Ca2+ signal are reported to be influenced by pH. The present study was designed to determine the effect of extracellular pH (pHo) and intracellular pH (pHi) on hormone-stimulated Ca2+ transport. We used rat pancreatic acini and measured free cytosolic Ca2+ concentration ([Ca2+]i) with fura-2, pHi with 2,7-bis(carboxyethyl)-5(6)-carboxyfluorescein (BCECF), and Ca2+ fluxes with 45Ca2+. In the presence of external Ca2+, increasing pHo increased steady-state [Ca2+]i during sustained agonist stimulation; in the absence of external Ca2+, this increase in [Ca2+]i did not occur. The addition of an antagonist or blocking plasma membrane Ca2+ influx with La3+ in stimulated cells suspended at pHo 8.2 resulted in a reduction in [Ca2+]i. Increasing pHo increased the rate and extent of 45Ca2+ uptake into stimulated cells and the rate and extent of Ca2+ reloading of intracellular stores. The increased Ca2+ content of the intracellular stores with increased pHo indicated that at physiological pHo and pHi the agonist-mobilizable internal stores are not saturated with Ca2+. Changes in pHo affected pHi. However, changes in pHi at constant pHo had no effect on hormone-evoked [Ca2+]i increase, reduction in [Ca2+]i after hormone stimulation, or reloading of intracellular stores. We conclude that the hormone-activated plasma membrane Ca2+ entry pathway responsible for Ca2+ reloading is directly modulated by external H+.

Topics: 4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid; 4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; Acetates; Acetic Acid; Amiloride; Ammonium Chloride; Animals; Atropine; Calcium; Calcium Radioisotopes; Carbachol; Hydrogen-Ion Concentration; In Vitro Techniques; Kinetics; Lanthanum; Pancreas; Rats; Rats, Inbred Strains; Sincalide

Erythrocyte lithium influx and efflux were investigated in vitro in patients with bipolar affective disorders and in age- and sex-matched healthy controls. To explore the components of lithium influx and efflux five selected inhibitors (ouabain, phloretin, p-chloromercury benzene sulfonate [PCMBS], 4,4'-diisothiocyano-2,2'-disulfonic acid stilbene, and lanthanium chloride) were employed. The mean values of lithium influx were similar in both populations of erythrocytes. The addition of ouabain and phloretin reduced lithium influx, but this effect was comparable in both patients and controls. PCMBS had an accelerating effect, and this was more pronounced in patients. Total erythrocyte lithium efflux from lithium-containing erythrocytes was comparable in both patients and controls. The addition of phloretin reduced RBC lithium efflux, the magnitude of this parameter, however, was similar in patients and controls. Erythrocyte lithium efflux was accelerated in the presence of PCMBS, and this effect was greater in patients. The relevance of these findings to the postulated cell membrane defect in affective disorders is evaluated.

Topics: 4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid; 4-Chloromercuribenzenesulfonate; 4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; Bipolar Disorder; Cell Membrane Permeability; Erythrocytes; Female; Humans; Lanthanum; Lithium; Male; Ouabain; Phloretin