Tachykinin NK1 and NK2 receptors mediate atropine-resistant ileal circular muscle contractions evoked by capsaicin

L. Barthó, Carlo A. Maggi, M. Wilhelm, Riccardo Patacchini

Research output: Article

26 Citations (Scopus)

Abstract

The atropine-resistant contractile action of the sensory stimulant drug capsaicin was examined on guinea-pig ileum circular muscle in vitro, with special regard to the involvement of endogenous tachykinins acting through tachykinin NK1 and NK2 receptors. A protocol, using rutheium red was developed for overcoming desensitization to capsaicin so that two two reproducible responses to this drug were obtained. Capsaicin (10-6 M) caused tonic and phasic contractions of the tissue. This effect was significantly inhibited by the tachykinin NK1 receptor blocking drug FK 888 (N2-[(4R)-4-hydroxy-1-(1-methyl-1H-indol-3-yl) carbonyl-L-prolyl]-N-methyl-N-phenylmethyl-3-(-2-naphthyl)-L-alaninamide) or the tachykinin NK2 receptor inhibitor GR 94, 800 (PhCO-Ala-Ala-D·Trp-Phe-D·Pro-Pro-NleNH2 (10-6 M each) and was practically abolished by the combine admministration of the two tac tachykinin receptor blockers. Likewise, the neuronal Na+ channel inhibitor tetrodotoxin abolished the response to capsaicin. It is concluded that the contractile effect of capsaicin in the circular muscle is predominantly mediated by tachykinin release and both subtypes of tachkinin receptor (NK1 and NK2) play an important role in this process. The source of tachykinin, however, is probably intrinsic neurons of the myenteric plexus, indirectly activated by capsaicin-sensitive nerves, as shown by the sensitivity of the response to tetrodotoxin.

Original languageEnglish
Pages (from-to)187-193
Number of pages7
JournalEuropean Journal of Pharmacology
Volume259
Issue number2
DOIs
Publication statusPublished - júl. 1 1994

Fingerprint

Tachykinins
Capsaicin
Muscle Contraction
Atropine
Tachykinin Receptors
Tetrodotoxin
Pharmaceutical Preparations
Myenteric Plexus
Muscles
Ileum
Guinea Pigs
Neurons

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Pharmacology

Cite this

Tachykinin NK1 and NK2 receptors mediate atropine-resistant ileal circular muscle contractions evoked by capsaicin. / Barthó, L.; Maggi, Carlo A.; Wilhelm, M.; Patacchini, Riccardo.

In: European Journal of Pharmacology, Vol. 259, No. 2, 01.07.1994, p. 187-193.

Research output: Article

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