Gq-linked NK(2) receptors mediate neurally induced contraction of human sigmoid circular smooth muscle

Gastroenterology. 2000 Jul;119(1):51-61. doi: 10.1053/gast.2000.8552.


Background & aims: Because tachykinins have been identified as neurotransmitters in the guinea pig colon and human ileum, we examined a possible role of tachykinin receptors and neurokinin (NK) A in neurally induced contraction of human sigmoid colon circular muscle.

Methods: Muscle strips were stimulated electrically for 10 seconds. Single cells were isolated by enzymatic digestion and permeabilized by saponin. [(35)S]GTPgammaS binding was assayed with or without NKA for 5 minutes. Intracellular Ca(2+) was measured using Fura 2.

Results: In the presence of 100 micromol/L L-NNA, 100 micromol/L atropine did not affect electrical field stimulation (EFS)-induced contraction. A peptide NK(2)-receptor antagonist (NK-2ra) but not an NK(1) antagonist FK888 (1 micromol/L) eliminated EFS-induced contraction. NKA-induced contraction in muscle strips and single cells was virtually abolished by NK-2ra, but not by FK888. In permeabilized cells, contraction was blocked by Gq-protein antibodies, but not by other G-protein antibodies, suggesting that NKA activates Gq, which was confirmed by a [(35)S]GTPgammaS binding assay. NKA-induced contraction and increase in cytosolic Ca(2+) were abolished by depletion of intracellular Ca(2+) stores.

Conclusions: Tachykinins may be the main excitatory neurotransmitters in human sigmoid circular muscle. NKA activates Gq-linked NK(2) receptors, which cause Ca(2+) release, followed by contraction.

Publication types

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

MeSH terms

  • Aged
  • Aged, 80 and over
  • Calcium / physiology
  • Colon / cytology
  • Colon / innervation
  • Colon / physiology*
  • Dipeptides / pharmacology
  • Electric Stimulation
  • Female
  • GTP-Binding Protein alpha Subunits, Gq-G11
  • GTP-Binding Proteins / metabolism*
  • Gastrointestinal Motility / drug effects
  • Gastrointestinal Motility / physiology*
  • Humans
  • In Vitro Techniques
  • Indoles / pharmacology
  • Intracellular Membranes / metabolism
  • Male
  • Middle Aged
  • Muscle, Smooth / innervation
  • Muscle, Smooth / physiology*
  • Nervous System Physiological Phenomena*
  • Neurokinin A / pharmacology
  • Receptors, Neurokinin-2 / agonists
  • Receptors, Neurokinin-2 / metabolism*


  • Dipeptides
  • Indoles
  • Receptors, Neurokinin-2
  • FK 888
  • Neurokinin A
  • GTP-Binding Proteins
  • GTP-Binding Protein alpha Subunits, Gq-G11
  • Calcium