The pharmacological action of MT-7

Pierluigi Onali, Abdu Adem, Evert Karlsson, Maria C. Olianas

Research output: Contribution to journalShort surveypeer-review

18 Scopus citations

Abstract

The mamba toxin MT-7 is the most selective ligand currently available for the muscarinic M1 receptor subtype. The toxin binds stably to the receptor and blocks the agonist-induced activation non-competitively. Although its mode of action on M1 receptors is not yet fully understood, some of the toxin properties support an allosteric mechanism. Thus, the toxin fails to elicit a complete inhibition of the binding of either the muscarinic antagonist [3H]N-methyl-scopolamine ([3H]NMS) or the agonist [3H]acetylcholine ([3H]ACh). When added to ligand-occupied M1 receptors, the toxin slows the dissociation rate of [3H]NMS and increases that of [3H]ACh. Site-directed mutagenesis studies have provided important information about the toxin amino acid residues which are critical for the stable binding to the receptor and for the allosteric modulation of antagonist dissociation. In vivo studies have shown that the intracerebral injection of MT-7 causes a long-lasting blockade of M1 receptor, thus providing a tool for the characterization of the functional role of this receptor subtype in discrete brain areas.

Original languageBritish English
Pages (from-to)1547-1552
Number of pages6
JournalLife Sciences
Volume76
Issue number14
DOIs
StatePublished - 18 Feb 2005

Keywords

  • Allosteric modulation
  • Dendroaspis angusticeps toxins
  • Muscarinic M receptor subtype

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