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The signaling of amitriptyline-induced inhibitory effect on electrical field stimulation response in colon smooth

Tin Sandar Zaw1, Phyu Phyu Khin1, Uy Dong Sohn2

  • 1Department of Pharmacology, College of Pharmacy, Chung-Ang University, Seoul, 156-756, Republic of Korea.

Naunyn-Schmiedeberg'S Archives of Pharmacology
|May 29, 2016
PubMed

Insights

Amitriptyline, an antidepressant, inhibits colon muscle contractions by affecting muscarinic receptors and a signaling pathway involving protein kinase C (PKC) and ATP-sensitive potassium channels.

Area of Science:

  • Pharmacology
  • Gastroenterology
  • Neuroscience

Background:

  • Amitriptyline is a tricyclic antidepressant with known effects on smooth muscle.
  • Its precise mechanism in regulating colon smooth muscle contraction is not fully understood.

Purpose of the Study:

  • To investigate the signaling pathway through which amitriptyline inhibits electrically stimulated rat colon smooth muscle contraction.
  • To identify the specific receptors and ion channels involved in amitriptyline's inhibitory effect.

Main Methods:

  • Isometric force of rat colon smooth muscle was measured using a polygraph.
  • Muscles were stimulated with electric field stimulation (EFS) and treated with cumulative doses of amitriptyline.
  • The effects of various antagonists and ion channel blockers were assessed to elucidate the mechanism of action.

Main Results:

  • Amitriptyline significantly inhibited EFS-induced colon smooth muscle contraction in a dose-dependent manner.
  • Inhibitory effects were enhanced by L-NAME, guanabenz, 5-HT4 receptor blockade, Rho-kinase inhibitor (Y27632), and MLCK inhibitor (ML9).
  • The effect was blocked by muscarinic antagonists, 5-HT receptor blockers, PLC inhibitor (U73122), PKC inhibitor (chelerythrine), and K+ channel blockers (TEA, glybenclamide). Nifedipine enhanced the effect.

Conclusions:

  • Amitriptyline inhibits colon smooth muscle contraction via EFS by blocking muscarinic receptors.
  • This action involves the PLC-mediated PKC pathway, ultimately leading to the opening of ATP-sensitive potassium channels.
Keywords:
AmitriptylineEFSInhibitory effectRat colon smooth muscle

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