Recombinant expression of a selective blocker of M(1) muscarinic receptors.
Mamba venoms contain peptides with high selectivity for muscarinic receptors. Due to the limited availability of the M(1) muscarinic receptor-selective MT7 or m1-toxin 1, the peptide was expressed in Sf9 cells using a synthetic cDNA and purified. The isolated peptide had over four orders of magnitude higher affinity for the M(1) compared to M(2)-M(5) muscarinic receptors. The peptide strongly inhibited Ca(2+) mobilisation through recombinant and endogenously expressed M(1) receptors, having no effect on the function of the other subtypes. The MT7 peptide provides a unique tool for identification and functional characterisation of M(1) receptors in cells and tissues.
Näsman
J
J
Department of Physiology, Uppsala University, BMC, Uppsala, S-751 23, Sweden. Johnny.Nasman@fysiologi.uu.se
Jolkkonen
M
M
Ammoun
S
S
Karlsson
E
E
Akerman
K E
KE
D000595:Amino Acid Sequence; D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D002460:Cell Line; D002614:Chelating Agents / Q000378:metabolism; D018679:Cholinergic Agonists / Q000494:pharmacology; D002852:Chromatography, Ion Exchange; D018076:DNA, Complementary / Q000378:metabolism; D004546:Elapid Venoms / Q000737:chemistry / Q000378:metabolism*; D016257:Fura-2 / Q000378:metabolism; D006801:Humans; D007313:Insecta; D008969:Molecular Sequence Data; D043643:Receptor, Muscarinic M1; D011976:Receptors, Muscarinic / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D014407:Tumor Cells, Cultured
D002614:Chelating Agents; D018679:Cholinergic Agonists; D018076:DNA, Complementary; D004546:Elapid Venoms; D043643:Receptor, Muscarinic M1; D011976:Receptors, Muscarinic; D011994:Recombinant Proteins; C083667:m1-toxin; D002217:Carbachol; D016257:Fura-2