Neurokinin3 receptor regulation of acetylcholine release from myenteric plexus

Am J Physiol. 1992 Nov;263(5 Pt 1):G659-64. doi: 10.1152/ajpgi.1992.263.5.G659.


This study sought to characterize the action of neurokinin B (NKB) and senktide, a selective synthetic agonist for NK3 receptors, on the myenteric plexus of the guinea pig small intestine. Both peptides stimulated a dose-dependent release of [3H]-acetylcholine (ACh). The mean effective dose values were 1 x 10(-9) for NKB and 3 x 10(-11) M for senktide. The action of these two neurokinins was blocked by the removal of Ca2+ and was sensitive to tetrodotoxin. The release of [3H]ACh was antagonized by omega-conotoxin GVIA, implying the involvement of N-type voltage-sensitive calcium channels. Senktide-evoked ACh release was also insensitive to nifedipine or flunarizine but was blocked by diltiazem. Treatment with protein kinase C (PKC) inhibitors (H-7 and polymyxin B) or activators (12-tetradecanoylphorbol 13-acetate and SC-9) failed to alter the NK3 receptor-mediated ACh output. Our data did not support an action mediated via PKC upon the activation of NK3 receptors on myenteric cholinergic neurons.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acetylcholine / metabolism*
  • Animals
  • Calcium / pharmacology
  • Calcium Channel Blockers / pharmacology
  • Enzyme Activation
  • Guinea Pigs
  • In Vitro Techniques
  • Myenteric Plexus / metabolism*
  • Neurokinin B / pharmacology
  • Peptide Fragments / pharmacology
  • Protein Kinase C / antagonists & inhibitors
  • Protein Kinase C / metabolism
  • Receptors, Neurokinin-3
  • Receptors, Neurotransmitter / metabolism
  • Receptors, Neurotransmitter / physiology*
  • Substance P / analogs & derivatives
  • Substance P / pharmacology
  • Tetrodotoxin / pharmacology


  • Calcium Channel Blockers
  • Peptide Fragments
  • Receptors, Neurokinin-3
  • Receptors, Neurotransmitter
  • senktide
  • Substance P
  • Tetrodotoxin
  • Neurokinin B
  • Protein Kinase C
  • Acetylcholine
  • Calcium