The pharmacological action of MT-7.
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.
Onali
Pierluigi
P
Section of Biochemical Pharmacology, Department of Neuroscience, University of Cagliari, 09042 Monserrato, Cagliari, Italy. onali@unica.it
Adem
Abdu
A
Karlsson
Evert
E
Olianas
Maria C
MC
D000818:Animals; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D018727:Muscarinic Antagonists / Q000494:pharmacology*; D009154:Mutation; D010455:Peptides / Q000494:pharmacology*; D043643:Receptor, Muscarinic M1 / Q000187:drug effects; D011976:Receptors, Muscarinic / Q000187:drug effects*
D036341:Intercellular Signaling Peptides and Proteins; C496907:MT-7 mamba toxin; D018727:Muscarinic Antagonists; D010455:Peptides; D043643:Receptor, Muscarinic M1; D011976:Receptors, Muscarinic