Inhibition of acetylcholine muscarinic M1 receptor function by the M1-selective ligand muscarinic toxin 7 (MT-7)

Maria C. Olianas, Carlo Maullu, Abdu Adem, Ezra Mulugeta, Evert Karlsson, Pierluigi Onali

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47 Citations (Scopus)


1 MT-7 (1 - 30 nM), a peptide toxin isolated from the venom of the green mamba Dendroaspis angusticeps and previously found to bind selectively to the muscarinic M1 receptor, inhibited the acetylcholine (ACh)-stimulated [35S]-guanosine-5'-O-(3-thio)triphosphate ([35S]-GTPγS) binding to membranes of Chinese hamster ovary (CHO) cells stably expressing the cloned human muscarinic M1 receptor subtype. 2 MT-7 failed to affect the ACh-stimulated [35S]-GTPγS binding in membranes of CHO cells expressing either the M2, M3 or M4 receptor subtype. 3 In N1E-115 neuroblastoma cells endogenously expressing the M1 and M4 receptor subtypes, MT-7 (0.3-3.0 nM) inhibited the carbachol (CCh)-stimulated inositol phosphates accumulation, but failed to affect the CCh-induced inhibition of pituitary adenylate cyclase activating polypeptide (PACAP) 38-stimulated cyclic AMP accumulation. 4 In both CHO/M1 and N1E-115 cells the MT-7 inhibition consisted in a decrease of the maximal agonist effect with minimal changes in the agonist EC50 value. 5 In CHO/M1 cell membranes, MT-7 (0.05-25 nM) reduced the specific binding of 0.05, 1.0 and 15 nm [3H]-N-methylscopolamine ([3H]-NMS) in a concentration-dependent manner, but failed to cause a complete displacement of the radioligand. Moreover, MT-7 (3 nM) decreased the dissociation rate of [3H]-NMS by about 5 fold. 6 CHO/M1 cell membranes preincubated with MT-7 (10 nM) and washed by centrifugation and resuspension did not recover control [3H]-NMS binding for at least 8 h at 30°C. 7 It is concluded that MT-7 acts as a selective noncompetitive antagonist of the muscarinic M1 receptors by binding stably to an allosteric site.

Original languageEnglish
Pages (from-to)447-452
Number of pages6
JournalBritish Journal of Pharmacology
Issue number3
Publication statusPublished - 2000
Externally publishedYes


  • Chinese hamster ovary cells
  • Cyclic AMP accumulation
  • Dendroaspis angusticeps toxin
  • Muscarinic receptor subtypes
  • N1E-115 cells
  • Noncompetitive antagonism
  • Phosphoinositide hydrolysis

ASJC Scopus subject areas

  • Pharmacology


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