The transient receptor potential vanilloid receptor 1, TRPV1 (VR1) inhibits peristalsis in the mouse jejunum.
BACKGROUND
The transient receptor potential vanilloid receptor 1, TRPV1 [previously termed the capsaicin or vanilloid receptor 1 (VR1)] is a nonselective cation channel that has been cloned and is expressed predominantly in sensory neurons. TRPV1 is activated by protons as well as capsaicin. Despite extensive research, the physiological function of TRPV1 in the gastrointestinal tract and other tissues remains elusive. We have examined the effect of the selective TRPV1-receptor ligand, capsaicin, on intestinal peristalsis by studying migrating motor complexes (MMCs).


METHODS
We performed experiments on Knockout mice (KO) in which the TRPV1 gene was disrupted using standard gene targeting techniques and their wildtype (WT) littermates. Jejunal contractile activity was recorded from in vitro segments of the jejunum, 4 - 5 cm in length. When distended to 2 - 3 cm with H2O, the segments generated regular MMCs that were recorded as changes in intraluminal pressure.


RESULTS
Capsaicin (1 - 100 nM) caused a dose-dependent inhibition of motility manifested as an increase in the interval between motor complexes (MCs) in the WT animal only, a response abolished by pre-treatment with TRPV1 antagonist capsazepine (Capz), ruthenium red (RR), and L-NAME. At higher doses of capsaicin (1 - 100 μM), periodic MCs were replaced by tonic increases in pressure upon which were superimposed continuous phasic contractions. This stimulation occurred in both KO and WT mice and was unaffected by pre-treatment with Capz, RR, and L-NAME.


CONCLUSIONS
These data demonstrate the potential role of TRPV1 receptors in organized peristalsis in the mouse jejunum. These findings also suggest that inhibition of contractions in mouse jejunum by TRPV1-receptor activation does involve a nitric oxide synthetase (NOS) pathway.
Department of Physiology, Gorgan Faculty of Medicine, Golestan University of Medical Science,Gorgan,Iran. Rahmati.r@gmail.com
Reza
R
Rahmati
D000818:Animals; D002211:Capsaicin / Q000494:pharmacology; D007583:Jejunum / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009569:Nitric Oxide / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000502:physiology; D010528:Peristalsis / Q000502:physiology*; D000074025:TRPA1 Cation Channel; D050916:TRPV Cation Channels / Q000502:physiology*; D050051:Transient Receptor Potential Channels / Q000502:physiology
D000074025:TRPA1 Cation Channel; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; D050051:Transient Receptor Potential Channels; C475685:Trpa1 protein, mouse; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D002211:Capsaicin