Conotoxin MI inhibits the alpha-delta acetylcholine binding site of the Torpedo marmorata receptor

Biochem Biophys Res Commun. 2002 Jul 26;295(4):791-5. doi: 10.1016/s0006-291x(02)00758-1.

Abstract

The muscle-type nicotinic receptor has two pharmacologically distinguishable acetylcholine binding sites at the alpha-gamma and alpha-delta subunit interfaces; alpha-conotoxins can bind them selectively. As reported, alpha-conotoxin MI has greater affinity for the site near the alpha-delta interface of the BC(3)H1 cell receptor but, in the case of the Torpedo californica receptor, displays greater affinity for that near the alpha-gamma interface. To further investigate ligand selectivity, we study the conotoxin MI-Torpedo marmorata receptor interaction. In this work, we show the binding of alpha-conotoxin MI to the T. marmorata receptor and the influence of the antagonist alpha-Bungarotoxin and the agonist carbamylcholine on such binding; in addition, and contrasting with the results for the Torpedo californica receptor, we identify the alpha-delta subunit interface as the high affinity binding site. This is the first work describing different characteristics of the interaction between alpha-conotoxin MI and receptors from different species of the same genus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholine / chemistry*
  • Acetylcholine / metabolism
  • Animals
  • Binding Sites
  • Binding, Competitive
  • Bungarotoxins / pharmacology
  • Carbachol / pharmacology
  • Conotoxins / pharmacology*
  • Dose-Response Relationship, Drug
  • Electrophoresis, Polyacrylamide Gel
  • Protein Binding
  • Receptors, Nicotinic / chemistry*
  • Receptors, Nicotinic / metabolism
  • Species Specificity
  • Torpedo / metabolism*

Substances

  • Bungarotoxins
  • Conotoxins
  • Receptors, Nicotinic
  • conotoxin MI
  • Carbachol
  • Acetylcholine