title: Effects of muscarinic toxins MT1 and MT2 from green mamba on different muscarinic cholinoceptors.
abstract: MT1 and MT2, polypeptides from green mamba venom, known to bind to muscarinic cholinoceptors, behave like muscarinic agonists in an inhibitory avoidance task in rats. We have further characterised their functional effects using different preparations. MT1 and MT2 behaved like relatively selective muscarinic M1 receptor agonists in rabbit vas deferens, but their effects were not reversed by washing or prevented by muscarinic antagonists, although allosteric modulators altered responses to MT1. Radioligand binding experiments indicated that both toxins irreversibly inhibited [3H]N-methylscopolamine binding to cloned muscarinic M1 and M4 receptors, and reduced binding to M5 subtype with lower affinity, while they reversibly inhibited the binding of [3H]prazosin to rat cerebral cortex and vas deferens, with 20 fold lower affinity. High concentrations of MT1 reversibly blocked responses of vas deferens to noradrenaline. MT1 and MT2 appear to irreversibly activate muscarinic M1 receptors at a site distinct from the classical one, and to have affinity for some alpha-adrenoceptors.
authors.affiliation: Department of Physiology and Pharmacology, and Strathclyde Institute for Drug Research, University of Strathclyde, 27 Taylor Street, Glasgow G4 ONR, United Kingdom. sidr@strath.ac.uk
authors.forename: Alan L
authors.initials: AL
authors.lastname: Harvey
authors.forename: Edgar
authors.initials: E
authors.lastname: Kornisiuk
authors.forename: Karen N
authors.initials: KN
authors.lastname: Bradley
authors.forename: Carlos
authors.initials: C
authors.lastname: Cerveñansky
authors.forename: Rosario
authors.initials: R
authors.lastname: Durán
authors.forename: Martin
authors.initials: M
authors.lastname: Adrover
authors.forename: Gonzalo
authors.initials: G
authors.lastname: Sánchez
authors.forename: Diana
authors.initials: D
authors.lastname: Jerusalinsky
mesh_terms: D000818:Animals; D003001:Cloning, Molecular; D017815:Elapidae; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D010455:Peptides / Q000378:metabolism / Q000633:toxicity*; D011485:Protein Binding; D011817:Rabbits; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism; D011976:Receptors, Muscarinic / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; D018340:Receptors, Adrenergic, alpha-1; D011976:Receptors, Muscarinic; C402142:mamba intestinal toxin 1; C089528:muscarinic toxin 3