ANTI-MUSCARINIC TOXINS FROM DENDROASPIS-ANGUSTICEPS

Toxins from the venom of the African green mamba, Dendroaspis angustic eps, fulfill a major need for selective ligands for some of the five g enetically defined subtypes of muscarinic acetylcholine receptors (m1- m5). Two toxins have been found that are highly selective antagonists for mi and m4 receptors (m1-toxin and m4-toxin, respectively). Two oth er toxins (MT1 and MT2) bind with high affinity to both mi and m4 rece ptors, and are agonists. Components of the venom also modify the bindi ng of radiolabeled antagonists to m2 receptors, but an m2-selective to xin has not yet been isolated. ml-Toxin can bind to m1 receptors at th e same time as typical competitive antagonists, suggesting that this t oxin binds to the N-terminal and outer loops of m1 receptor molecules, rather than within the receptor pocket where typical agonists and ant agonists bind. The binding of toxins to the outer parts of receptor mo lecules probably accounts for their much higher specificity for indivi dual receptor subtypes than is seen with smaller ligands. Toxins are u seful for identifying, counting, localizing, activating and blocking m 1 and m4 receptors with high specificity. Copyright (C) 1996 Elsevier Science Ltd