Interaction of myasthenic immunoglobulins and cholinergic agonists on acetylcholine receptors of rat myotubes.
Acetylcholine receptor (AChR) antibodies from patients with myasthenia gravis (MG) impair neuromuscular transmission by altering the number of AChRs at the skeletal muscle motor endplate. Cholinergic agonists similarly impair transmission by altering the number and affinity of AChRs. The frequent clinical resistance ot anticholinesterase medication in patients with MG has raised the question of possible synergistic effects of these agents on regulation of AChRs and neuromuscular transmission. To investigate this question, rat myotube cultures were incubated with MG globulin and carbamylcholine (CMC) for 20 hours. The number of AChRs was assayed by 125I-alpha-bungarotoxin binding. Incubation of cultures with both MG globulins and CMC consistently produced greater reductions of AChRs than incubation with either substance alone. Cholinergic antagonists blocked the CMC effect but not the MG globulin effect. A muscarinic antagonist had no effect. The effects of short-term incubation with these substances on the affinity of AChR were assessed by the rate of 125I-alpha-bungarotoxin-AChR complex formation. CMC desensitized AChRs, but MG globulins did not alter the affinity of AChRs. Results with this in vitro model suggest that chronic anticholinesterase therapy in the presence of MG AChR antibodies may aggravate failure of neuromuscular transmission in MG.
D000818:Animals; D002038:Bungarotoxins / Q000378:metabolism; D002217:Carbachol / Q000494:pharmacology*; D046508:Culture Techniques; D004305:Dose-Response Relationship, Drug; D007074:Immunoglobulin G / Q000276:immunology; D007136:Immunoglobulins / Q000276:immunology*; D009132:Muscles / Q000187:drug effects; D009157:Myasthenia Gravis / Q000276:immunology*; D009469:Neuromuscular Junction / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D011950:Receptors, Cholinergic / Q000187:drug effects* / Q000276:immunology; D011978:Receptors, Nicotinic; D009435:Synaptic Transmission / Q000187:drug effects; D064569:alpha7 Nicotinic Acetylcholine Receptor
D002038:Bungarotoxins; C579165:Chrna7 protein, rat; D007074:Immunoglobulin G; D007136:Immunoglobulins; D011950:Receptors, Cholinergic; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; D002217:Carbachol