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Interaction of mercury compounds with muscarinic receptor subtypes in the rat brain.

The in vitro effects of mercuric chloride (HgCl2) and methylmercury (CH3HgOH) on the M1 and M2 muscarinic receptor subtypes were investigated in rat brain cortical membranes. HgCl2 and CH3HgOH were almost equipotent in inhibiting the binding of [3H]telenzepine to M1 receptors (IC50s = 2.2 and 3.4 microM, respectively). Conversely, HgCl2 was a thirty-fold more potent inhibitor of [3H]AF-DX 384 binding to M2 sites than CH3HgOH (lC50s = 5 and 149 microM, respectively). In all cases HgCl2 showed steep and monophasic inhibition curves, whereas those of CH3HgOH were biphasic (M1) or shallow (M2). CH3HgOH-induced inhibition of both [3H]telenzepine and [3H]AF-DX 384 binding was of the competitive type, while HgCl2 caused a pronounced reduction of the Bmax value associated with a small change in affinity. CH3HgOH also decreased the affinity of the agonist carbachol for M1 and M2 receptors, while inorganic mercury had minimal effects on the carbachol dose-response curves. These results indicate that inorganic and organic mercury differ in their interaction with muscarinic receptor subtypes and that M1 receptors may represent a preferential target for their effects.

Animals↗
PubMed2005

Organic mercury compounds and autoimmunity.

Based on in vitro studies and short-term in vivo studies, all mercurials were for a long time considered as prototypic immunosuppressive substances. Recent studies have confirmed that organic mercurials such as methyl mercury (MeHg) and ethyl mercury (EtHg) are much more potent immunosuppressors than inorganic mercury (Hg). However, Hg interacts with the immune system in the presence of a susceptible genotype to cause immunostimulation, antinucleolar antibodies targeting fibrillarin, and systemic immune-complex (IC) deposits, a syndrome called Hg-induced autoimmunity (HgIA). Recent studies in mice with a susceptible genotype has revealed that the immunosuppressive effect of MeHg and EtHg will within 1-3 weeks be superseded by immunostimulation causing an HgIA-like syndrome. At equimolar doses of Hg, MeHg has the weakest immunostimulating, autoimmunogen, and IC-inducing effect, while the effect of thimerosal is similar to that of inorganic mercury. The immunosuppression is caused by the organic mercurials per se. Since they undergo rapid transformation to inorganic Hg, studies are being undertaken to delineate the importance of the organic substances per se and the newly formed inorganic Hg for induction of autoimmunity.

Animals↗
PubMed2001

Cytotoxicity of dental composite components and mercury compounds in lung cells.

OBJECTIVE: The effect of dental composite components triethyleneglycoldimethacrylate (TEGDMA) and hydroxyethylmethacrylate (HEMA), as well as mercuric chloride (HgCl2) and methylmercury chloride (MeHgCl) was investigated on the release of lactatedehydrogenase (LDH) from alveolar epithelial lung cell lines in vitro. METHODS: The confluent cell layers from the A549 (human, malignant) and the L2 cells (rat) were incubated with various concentrations of HEMA, TEGDMA, MeHgCl and HgCl2 at 37 degrees C in 2% (v/v) CO2 atmosphere for 8h. In further experiments the L2 cells were incubated with the same compounds for 6-48 h. LDH release was measured and the values were expressed as percentage of the LDH content. The values were plotted on a concentration log-scale and the substance concentration at the maximum slope was assessed as effective concentration (EC50). RESULTS: A significant (p<0.05) increase in the LDH release was found in the L2 cells after 8-h incubation with HEMA (4 mmol/l), TEGDMA (2 mmol/l), MeHgCl (0.01 mmol/l) and HgCl2 (0.015 mmol/l), and in A549 cells with HEMA (14 mmol/l), TEGDMA (15 mmol/l), MeHgCl (0.15 mmol/l) and HgCl2 (0.05 mmol/l), compared to controls. The EC50 values from compounds in the L2 cells are shown in the following table (mean; sem in parentheses; n=3-6; #n=1): [see text]. SIGNIFICANCE: The toxic effect of HgCl2 and MeHgCl from the L2 cells was about 100-700-fold higher than of the dental composite components. A significant (p<0.05) time dependent increase of toxicity was observed with TEGDMA, HEMA and MeHgCl.

Animals↗
PubMed1986

Experimental neuropathy induced by methyl mercury compounds: autoradiographic study of GABA uptake by dorsal root ganglia.

Methyl mercury chloride (MMC, 10 mg/kg body weight/day) was subcutaneously injected into rats for 1 week. Animals were killed at 5 or 14 days (at the onset of clinical symptoms) after injection of MMC. Morphologically, most of the myelinated fibers in peripheral nerves showed axonal degeneration. Ganglion cells showed histopathological changes similar to those in previous reports. The cytoplasm of satellite cells stained dark with toluidine blue and was narrow, and sometimes showed focal disappearance of rough endoplasmic reticula, ribosomes or filaments. Autoradiography in the control rats showed that 3H-GABA was exclusively localized within the satellite cells and Schwann cell cytoplasm of the myelinated fibers and was not revealed within the ganglion cells. The number of silver grains markedly decreased in the satellite cells of the MMC-treated rats. 14C-GABA uptake by dorsal root ganglia also decreased to 75.0% of the control on the 5th day and to 49.2% on the 14th day. Therefore, MMC was found to inhibit greatly the GABA uptake into the satellite cells in the earlier stage of poisoning, and was considered to affect primarily the satellite cells and Schwann cells as well as the ganglion cells.

Animals↗