Effects of muscarinic toxins MT1 and MT2 from green mamba on different muscarinic cholinoceptors

Alan L Harvey, Edgar Kornisiuk, Karen N Bradley, Carlos Cerveñansky, Rosario Durán, Martin Adrover, Gonzalo Sánchez, Diana Jerusalinsky

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31 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)1543-1554
Number of pages12
JournalNeurochemical Research
Volume27
Issue number11
DOIs
Publication statusPublished - Nov 2002

Keywords

  • animals
  • molecular cloning
  • elapidae
  • male
  • peptides
  • protein binding
  • rabbits
  • radioligand assay
  • rats
  • receptors adrenergic alpha-1
  • receptors muscarinic
  • wistar

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