Acetylcholine receptor degradation: study of mechanism of action of inhibitory drugs.
The continuous muscle cell line BC3-H1, which expresses nicotinic Acetylcholine receptors (AChR) at the cell surface, was used to study the effect of lysosomotropic drugs on AChR degradation both in the normal condition and after stimulation induced by treatment with anti-AChR antibodies. We found that ammonium chloride, methylamine, and bacitracin decreased AChR degradation both in normal and stimulated cells but did not prevent AChR internalization from the cell surface. In addition NH4Cl increased size and number of lysosomes in treated cells, while methylamine and bacitracin did not. These latter drugs increased the Golgi area and the vesicular complement of the Golgi apparatus. It is proposed that the drugs used decrease AChR degradation by interfering either with lysosome function, or with the fusion of endosomes with lysosomes. The data also suggest that AChR degradation induced by anti-AChR antibodies is carried out by a mechanism similar to that accounting for AChR degradation in control cells.
D000643:Ammonium Chloride / Q000494:pharmacology; D001414:Bacitracin / Q000494:pharmacology; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D008744:Methylamines / Q000494:pharmacology; D008854:Microscopy, Electron; D009132:Muscles / Q000378:metabolism / Q000648:ultrastructure; D011950:Receptors, Cholinergic / Q000378:metabolism*; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*
D007074:Immunoglobulin G; D008744:Methylamines; D011950:Receptors, Cholinergic; D011978:Receptors, Nicotinic; D000643:Ammonium Chloride; D001414:Bacitracin; C027451:methylamine