TY - JOUR
T1 - Involvement of TRPV1-dependent and -independent components in the regulation of vagally induced contractions in the mouse esophagus
AU - Boudaka, Ammar
AU - Wörl, Jürgen
AU - Shiina, Takahiko
AU - Neuhuber, Winfried L.
AU - Kobayashi, Haruo
AU - Shimizu, Yasutake
AU - Takewaki, Tadashi
N1 - Funding Information:
We thank Prof. Makoto Tominaga (National Institutes of Natural Sciences, Okazaki, Japan) for the helpful and stimulating discussions. This work was supported by a travel grant to J.W. from the Chihiro and Kiyoko Yokochi Found, Kanehara Ichiro Foundation in Tokyo, Japan.
PY - 2007/2/5
Y1 - 2007/2/5
N2 - Transient receptor potential ion channel of the vanilloid type 1 (TRPV1)-dependent pathway, consisting of capsaicin-sensitive tachykininergic primary afferent and myenteric nitrergic neurons, has been suggested to mediate the inhibitory effect of capsaicin on vagally mediated striated muscle contractions in the rat esophagus. In a recent study, similar but also different effects of capsaicin and piperine on TRPV1 were demonstrated. Therefore, this study aimed to compare the effects of these two drugs on vagally induced contractions in the mouse esophagus. Capsaicin and piperine inhibited vagally induced contractions of a thoracic esophageal segment in a concentration-dependent manner. Ruthenium red (10 μM; a non-selective blocker of transient receptor potential cation channels) and SB-366791 (10 μM; a novel selective antagonist of TRPV1) blocked the inhibitory effect of capsaicin but not that of piperine. Piperine inhibited the vagally mediated contractions in esophagi of adult mice neonatally injected with capsaicin, while capsaicin failed to do so. Desensitization of TRPV1 in the mouse esophagus by in vitro pretreatment with capsaicin failed to affect the inhibitory effect of piperine, whereas the piperine effect was cross-desensitized by capsaicin pretreatment in rat and hamster esophagi. Additionally, a tachykinin NK1 receptor antagonist, L-732,138 (1 μM), as well as a nitric oxide synthase inhibitor, NG-nitro-l-arginine methyl ester (l-NAME 200 μM), blocked the inhibitory effect of capsaicin but not that of piperine. Taken together, the results suggest that piperine inhibits the vagally mediated striated muscle contraction in the mouse esophagus through its action on a TRPV1-dependent pathway as well as a TRPV1-independent site.
AB - Transient receptor potential ion channel of the vanilloid type 1 (TRPV1)-dependent pathway, consisting of capsaicin-sensitive tachykininergic primary afferent and myenteric nitrergic neurons, has been suggested to mediate the inhibitory effect of capsaicin on vagally mediated striated muscle contractions in the rat esophagus. In a recent study, similar but also different effects of capsaicin and piperine on TRPV1 were demonstrated. Therefore, this study aimed to compare the effects of these two drugs on vagally induced contractions in the mouse esophagus. Capsaicin and piperine inhibited vagally induced contractions of a thoracic esophageal segment in a concentration-dependent manner. Ruthenium red (10 μM; a non-selective blocker of transient receptor potential cation channels) and SB-366791 (10 μM; a novel selective antagonist of TRPV1) blocked the inhibitory effect of capsaicin but not that of piperine. Piperine inhibited the vagally mediated contractions in esophagi of adult mice neonatally injected with capsaicin, while capsaicin failed to do so. Desensitization of TRPV1 in the mouse esophagus by in vitro pretreatment with capsaicin failed to affect the inhibitory effect of piperine, whereas the piperine effect was cross-desensitized by capsaicin pretreatment in rat and hamster esophagi. Additionally, a tachykinin NK1 receptor antagonist, L-732,138 (1 μM), as well as a nitric oxide synthase inhibitor, NG-nitro-l-arginine methyl ester (l-NAME 200 μM), blocked the inhibitory effect of capsaicin but not that of piperine. Taken together, the results suggest that piperine inhibits the vagally mediated striated muscle contraction in the mouse esophagus through its action on a TRPV1-dependent pathway as well as a TRPV1-independent site.
KW - (Mouse)
KW - (Rat)
KW - Capsaicin
KW - Esophageal motility
KW - Esophagus
KW - Piperine
KW - Primary afferent neuron
KW - Striated muscle
KW - TRPV1
KW - Vagus nerve
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U2 - 10.1016/j.ejphar.2006.11.005
DO - 10.1016/j.ejphar.2006.11.005
M3 - Article
C2 - 17156774
AN - SCOPUS:33846041612
SN - 0014-2999
VL - 556
SP - 157
EP - 165
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
IS - 1-3
ER -