Regeneration of functionally active rat brain muscarinic receptor in vitro after inhibition with methylmercury chloride]

The effect of methylmercury on muscarinic receptors and the regeneration of functionally active muscarinic receptor in vitro by antagonists were investigated. The result showed that methylmercury chloride (MMC) inhibited the binding of 3H] QNB to muscarinic receptor of rat brain-lysed synaptosomes, with IC50 values of 4.18 mmol/L. Regeneration of functionally active rat brain muscarinic receptors after inhibition with methylmercury was achieved by 2,3-dimercapto-1-propanesulfonc acid, Na salt (DMPS) dithiothreitol (DTT), glutathione (GSH) and Cysteine. Blocking the sulfhydryl groups is suggested to be the molecular mechanism of inhibition of brain muscarinic receptors by methylmercury. Our results provide evidence that thiols chelate out mercuric cations that tightly bound to sulfhydryl groups in muscarinic receptor binding sites and regenerate 3H] QNB binding activity.