Functional study on TRPV1‐mediated signalling in the mouse small intestine: involvement of tachykinin receptors

Afferent nerves in the gut not only signal to the central nervous system but also provide a local efferent‐like effect. This effect can modulate intestinal motility and secretion and is postulated to involve the transient receptor potential of the vanilloid type 1 (TRPV1). By using selective TRPV1 a...

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Published in:Neurogastroenterology and motility 2008-05, Vol.20 (5), p.546-556
Main Authors: De Man, J. G., Boeckx, S., Anguille, S., De Winter, B. Y., De Schepper, H. U., Herman, A. G., Pelckmans, P. A.
Format: Article
Language:English
Subjects:
afferent nerves
Animals
BCTC
capsaicin
Capsaicin - pharmacology
Dose-Response Relationship, Drug
Intestine, Small - drug effects
Intestine, Small - physiology
Mice
Muscle Contraction - drug effects
Muscle Contraction - physiology
Receptors, Tachykinin - physiology
Signal Transduction - drug effects
Signal Transduction - physiology
tachykinin
TRPV Cation Channels - physiology
TRPV1
vanilloid
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Summary:Afferent nerves in the gut not only signal to the central nervous system but also provide a local efferent‐like effect. This effect can modulate intestinal motility and secretion and is postulated to involve the transient receptor potential of the vanilloid type 1 (TRPV1). By using selective TRPV1 agonist and antagonists, we studied the efferent‐like effect of afferent nerves in the isolated mouse jejunum. Mouse jejunal muscle strips were mounted in organ baths for isometric tension recordings. Jejunal strips contracted to the TRPV1 agonist capsaicin. Contractions to capsaicin showed rapid tachyphylaxis and were insensitive to tetrodotoxin, hexamethonium, atropine or l‐nitroarginine. Capsaicin did not affect contractions to electrical stimulation of enteric motor nerves and carbachol. Tachykinin NK1, NK2 and NK3 receptor blockade by RP67580, nepadutant plus SR‐142801 reduced contractions to capsaicin to a similar degree as contractions to substance P. The effect of the TRPV1 antagonists capsazepine, SB‐366791, iodo‐resiniferatoxin (iodo‐RTX) and N‐(4‐tertiarybutylphenyl)‐4‐(3‐cholorphyridin‐2‐yl)tetrahydropyrazine‐1(2H)‐carbox‐amide (BCTC) was studied. Capsazepine inhibited contractions not only to capsaicin but also those to carbachol. SB‐366791 reduced contractions both to capsaicin and carbachol. Iodo‐RTX partially inhibited the contractions to capsaicin without affecting contractions to carbachol. BCTC concentration‐dependently inhibited and at the highest concentration used, abolished the contractions to capsaicin without affecting those to carbachol. From these results, we conclude that activation of TRPV1 in the mouse intestine induces a contraction that is mediated by tachykinins most likely released from afferent nerves. The TRPV1‐mediated contraction does not involve activation of intrinsic enteric motor nerves. Of the TRPV1 antagonists tested, BCTC combined strong TRPV1 antagonism with TRPV1 selectivity.
ISSN:1350-1925
1365-2982
DOI:10.1111/j.1365-2982.2007.01064.x