Penicillamine-induced myasthenia gravis: effects of penicillamine on acetylcholine receptor

Autoimmune diseases, including myasthenia gravis, occur in patients treated with D-penicillamine. Because D-penicillamine might induce autoantibodies by the mechanism of antigenic alteration, we studied the reaction of D-penicillamine with purified acetylcholine receptor from Torpedo californica. We found that brief exposure to D-penicillamine resulted in its covalent attachment to two receptor subunits, alpha (40,000 daltons) and gamma (59,000 daltons), presumably by reduction and formation of mixed disulfides. Furthermore, D-penicillamine treatment resulted in a dramatic modification of the equilibrium acetylcholine binding properties of both purified receptor and receptor-rich membrane fragments.