Protective effect of dimercaptosuccinic acid on methylmercury and mercuric chloride inhibition of rat brain muscarinic acetylcholine receptors |
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| Authors: | EAM Abdallah AE Shamoo |
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| Institution: | Membrane Biochemistry Research Laboratory, Department of Biological Chemistry, University of Maryland, School of Medicine, Baltimore, Maryland 21201 USA |
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| Abstract: | The reactivation of the rat brain muscarinic acetylcholine receptor (mACh-R) binding with dimercaptosuccinic acid (DMSA) after in vitro and in vivo inhibition by mercuric chloride (HgCl2) and methylmercuric chloride (MeHg) was investigated. Receptor binding was estimated by the potent and specific antagonist l-3H]quinuclidinyl benzilate (3H]QNB). Rat brain synaptosomal membranes were exposed to HgCl2 and MeHg. At 1 × 10?4M. HgCl2 caused complete inhibition of the 3H]QNB binding. The inhibition of 3H]QNB binding by HgCl2 was still higher than 50% at 1 × 10?8M. MeHg caused less inhibition of 3H]QNB binding than HgCl2. The inhibited receptors showed a significant degree of reactivation when treated with DMSA. The recovery was almost complete after MeHg inhibition or with the lower HgCl2 concentrations. Generally, the reactivation was dependent on the concentration of DMSA. When rats injected with either early or delayed doses of DMSA following administration with five consecutive daily doses (8 mg/kg body wt, Gavage method) of MeHg or HgCl2, the inhibition of 3H]QNB binding was less than untreated ones. The early treatment with DMSA decreased the inhibition of 3H]QNB binding due to MeHg or HgCl2 intoxication. However, DMSA was more effective in reducing HgCl2 inhibition than MeHg either in vitro or in vivo treatment. The ability of DMSA to reactivate the mACh-R after inhibition with the mercurials emphasizes the involvement of essential sulfhydryl groups in 3H]QNB binding sites, and also shows that these sulfhydryl groups are the primary target for the MeHg and HgCl2 inhibition of the rat brain muscarinic receptors. |
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| Keywords: | To whom all correspondence and requests for reprints should be addressed |
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