Thimerosal: a versatile sulfhydryl reagent, calcium mobilizer, and cell function-modulating agent.
نویسنده
چکیده
An overview of the literature concerning the effects of thimerosal is presented. Because of its antibacterial effect, thimerosal is used for a variety of practical purposes such as antiseptic and preservative. In biomedical studies, thimerosal is used as a sulfhydryl reagent, and as a calcium-mobilizing agent. The ability of thimerosal to act as a sulfhydryl group is related to the presence of mercury. Relatively little study has been devoted to the mechanism of the reaction of thimerosal with the sulfhydryl group; the sulfhydryl reactive capacity is mostly concluded on the basis of inactivation of the effect by dithiothreitol (DTT). Thimersal causes a release of calcium from intracellular stores in many cells types; this is followed by an influx of extracellular calcium. Both InsP3- and ryanodine-sensitive calcium stores may be affected. Studies with permeabilized cells or organelles show that the effect of thimerosal on calcium is dependent on the concentration: low concentrations of thimerosal stimulate calcium release, high concentrations are inhibitory. This dependence is not found in intact cells. Thimerosal may activate or inhibit a number of cell functions. These are often related to the ability to release calcium or with the sulfhydryl reactivity. In platelets, thimerosal causes aggregation, increase of arachidonic acid metabolism, and exocytotic release of serotonin. In neutrophils, thimerosal causes, besides an increase of cytosolic free calcium, an increase of formyl-methionyl-leucyl-phenylalanine (fMLP)-activated leukotriene release, and a modulation of chemotactic migration and exocytosis. At low concentrations, thimerosal induces chemotactic migration of neutrophils, in the absence of other chemoattractants. The effect is also observed with thiosalicylic acid, indicating that the stimulation of migration was due to the thiosalicylic acid moiety of the thimerosal molecule. At higher concentrations, thimerosal causes inhibition of fMLP-activated migration. Low concentrations of thimerosal, but not of thiosalicylic acid, induced exocytotic enzyme release from neutrophils. High concentrations of thimerosal inhibited fMLP-activated exocytosis. The results point to an involvement of calcium mobilization and calcium influx of activation, and reaction with sulfhydryl groups for inhibition.
منابع مشابه
Ca(2+)-induced Ca2+ release in insulin-secreting cells.
The sulphydryl reagent thimerosal (50 microM) released Ca2+ from a non-mitochondrial intracellular Ca2+ pool in a dose-dependent manner in permeabilized insulin-secreting RINm5F cells. This release was reversed after addition of the reducing agent dithiothreitol. Ca2+ was released from an Ins(1,4,5)P3-insensitive pool, since release was observed even after depletion of the Ins(1,4,5)P3-sensitiv...
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Thimerosal, a sulfhydryl oxidizing reagent, has been shown to induce Ca2+ mobilization in several cell types and to increase the sensitivity of intracellular Ca2+ stores to inositol 1,4,5-trisphosphate (IP3). Using purified IP3 receptor (IP3R) protein reconstituted in vesicles, we demonstrate pronounced stimulation by thimerosal of its Ca2+ channel activity. Effects of thimerosal are dependent ...
متن کاملInhibitory action of thimerosal, a sulfhydryl oxidant, on sodium channels in rat sensory neurons.
The effects of thimerosal, a sulfhydryl oxidizing agent, on tetrodotoxin-sensitive (TTX-S) and tetrodotoxin-resistant (TTX-R) sodium channels in rat dorsal root ganglion neurons were studied using the whole-cell patch clamp technique. Thimerosal blocked the two types of sodium channels in a dose-dependent manner. The inhibitory effect of thimerosal was much more pronounced in TTX-R sodium chann...
متن کاملThe effect of thimerosal on neutrophil migration: a comparison with the effect on calcium mobilization and CD11b expression.
The sulfhydryl-reactive compound thimerosal caused a chemotactic stimulation of neutrophil migration at low concentrations and inhibition of chemoattractant-stimulated chemotaxis at high concentrations. Thiosalicylic acid, an analog of thimerosal devoid of mercury, also stimulated migration at low concentrations and caused inhibition at higher concentrations, though the inhibitory effect was le...
متن کاملPurified Reconstituted Inositol 1,4,5-Trisphosphate Receptors
Thimerosal, a sulfhydryl oxidizing reagent, has been shown to induce Ca2+ mobilization in several cell types and to increase the sensitivity of intracellular Ca2+ stores to inositol 1,4,54risphosphate (IP,). Using purified IP, receptor (IP,R) protein reconstituted in vesicles, we demonstrate pronounced stimulation by thimerosal of its Ca2+ channel activity. Effects of thimerosal are dependent o...
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ورودعنوان ژورنال:
- General pharmacology
دوره 33 1 شماره
صفحات -
تاریخ انتشار 1999