BIOMEDICAL APPLICATION OF SNAKE-VENOM NEUROTOXINS - ACETYLCHOLINE-RECEPTOR AND MYASTHENIA-GRAVIS

The venom of many of the snakes of the Elapidae and Hydrophiidae is hi ghly toxic, producing flaccid paralysis and respiratory failure in ani mals. These effects mainly are attributable to postsynaptic neurotoxin s known to bind specifically and tightly to the nicotinic acetylcholin e receptor(AChR). Sequence analyses findings for postsynaptic neurotox ins from many snake species show they can be classified into short (61 -62 amino acid residues) and long (71-74 amino acid residues) neurotox ins. Short-chain neurotoxins bind specifically, but weakly to AChRs, a nd the binding is slowly reversible. This property makes them particul arly useful for the purification of AChRs. Long-chain neurotoxons, suc h as alpha-Bungarotoxin (alpha-BuTx), bind specifically and tightly to AChRs and are useful as probes to measure the number of AChRs in the bound radioiodinated neurotoxin contents. The most common clinical app lication of neurotoxin is in the detection of nicotinic AChRs and thei r antibodies in research related to the pathogenesis of myasthenia gra vis (MG). We have developed new assay systems for detecting antibodies that recognize different antigenic determinants in AChR protein. Usin g them, we detected a markedly high prevalence of anti-AChR antibodies in MG. This determination now allows for a definite diagnosis of MG. We also show that the blocking effect of the anti-AChR antibodies in M G sera is due to steric hindrance caused by their binding to a region other than that for alpha-BuTx.