Activation of M2 muscarinic receptors in guinea-pig ileum opens cationic channels modulated by M3 muscarinic receptors

Life Sci. 1997;60(13-14):1121-8. doi: 10.1016/s0024-3205(97)00056-8.


In longitudinal muscle of guinea-pig ileum, activation of muscarinic receptors causes contraction antagonised by M3 receptor subtype antagonists despite a preponderance of M2 receptor subtype binding sites. Experiments on single smooth muscle cells under voltage-clamp described here show that the cationic current evoked by carbachol which normally causes depolarization of the muscle is inhibited competitively by M2 antagonists with affinities typical of antagonism at a M2 receptor. However, M3 antagonists strongly reduced the maximum cationic current which could be evoked by carbachol in a non-competitive manner with affinities typical for an action at M3 receptors. Thus cation channels are gated by M2 receptor activation but strongly modulated by activation of M3 receptors.

MeSH terms

  • Animals
  • Carbachol / pharmacology
  • Guinea Pigs
  • Ileum / drug effects
  • Ileum / physiology*
  • In Vitro Techniques
  • Ion Channels / physiology*
  • Muscarinic Antagonists / pharmacology
  • Muscle Contraction / drug effects
  • Receptor, Muscarinic M2
  • Receptor, Muscarinic M3
  • Receptors, Muscarinic / physiology*


  • Ion Channels
  • Muscarinic Antagonists
  • Receptor, Muscarinic M2
  • Receptor, Muscarinic M3
  • Receptors, Muscarinic
  • Carbachol