TY - JOUR
T1 - Involvement of TRPV2 activation in intestinal movement through nitric oxide production in mice
AU - Mihara, Hiroshi
AU - Boudaka, Ammar
AU - Shibasaki, Koji
AU - Yamanaka, Akihiro
AU - Sugiyama, Toshiro
AU - Tominaga, Makoto
PY - 2010/12/8
Y1 - 2010/12/8
N2 - Transient receptor potential channel vanilloid 2 (TRPV2) can detect various stimuli such as temperature (>52°C), stretch, and chemicals, including 2-aminoethoxydiphenyl borate, probenecid, and lysophospholipids. Although expressed in many tissues, including sensory and motor neurons, TRPV2 expression and function in the gastrointestinal tract is poorly understood. Here, we show TRPV2 expression in the murine intestine and its involvement in intestinal function. Almost all mouse intestinal intrinsic sensory and inhibitory motor neurons, both cell bodies and nerve fibers, showed TRPV2 immunoreactivity. Several known TRPV2 activators increased cytosolic Ca2+ concentrations and evoked TRPV2-like current responses in dissociated myenteric neurons. Interestingly, mechanical stimuli activated inward currents in a strength-dependent manner, which were inhibited by a TRPV2 inhibitor tranilast. TRPV2 activation in isolated intestine inhibited spontaneous circular muscle contraction, which did not occur in the presence of the TRPV2 antagonist, tetrodotoxin or nitro oxide (NO) synthase pathway inhibitors. Also, increased intestinal NO production was observed in response to a TRPV2 agonist, and gastrointestinal transit in vivo was accelerated by TRPV2 agonists or an NO donor. In conclusion, TRPV2 may contribute to intestinal motility through NO production, and TRPV2 is a promising target for controlling intestinal movement.
AB - Transient receptor potential channel vanilloid 2 (TRPV2) can detect various stimuli such as temperature (>52°C), stretch, and chemicals, including 2-aminoethoxydiphenyl borate, probenecid, and lysophospholipids. Although expressed in many tissues, including sensory and motor neurons, TRPV2 expression and function in the gastrointestinal tract is poorly understood. Here, we show TRPV2 expression in the murine intestine and its involvement in intestinal function. Almost all mouse intestinal intrinsic sensory and inhibitory motor neurons, both cell bodies and nerve fibers, showed TRPV2 immunoreactivity. Several known TRPV2 activators increased cytosolic Ca2+ concentrations and evoked TRPV2-like current responses in dissociated myenteric neurons. Interestingly, mechanical stimuli activated inward currents in a strength-dependent manner, which were inhibited by a TRPV2 inhibitor tranilast. TRPV2 activation in isolated intestine inhibited spontaneous circular muscle contraction, which did not occur in the presence of the TRPV2 antagonist, tetrodotoxin or nitro oxide (NO) synthase pathway inhibitors. Also, increased intestinal NO production was observed in response to a TRPV2 agonist, and gastrointestinal transit in vivo was accelerated by TRPV2 agonists or an NO donor. In conclusion, TRPV2 may contribute to intestinal motility through NO production, and TRPV2 is a promising target for controlling intestinal movement.
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U2 - 10.1523/JNEUROSCI.4426-10.2010
DO - 10.1523/JNEUROSCI.4426-10.2010
M3 - Article
C2 - 21147993
AN - SCOPUS:78650048949
SN - 0270-6474
VL - 30
SP - 16536
EP - 16544
JO - Journal of Neuroscience
JF - Journal of Neuroscience
IS - 49
ER -