TY - JOUR
T1 - Combined determination with functional and morphological studies of origin of nerve fibers expressing transient receptor potential vanilloid 1 in the myenteric plexus of the rat jejunum
AU - Kadowaki, Makoto
AU - Kuramoto, Hirofumi
AU - Takaki, Miyako
N1 - Funding Information:
The authors are grateful to medical students of Nara Medical University, Kai Yamazaki, Hiroko Hashimoto, Natsuko Imakita, Natsuko Kitagawa, Satoko Sugizaki for their technical assistant. We thank Dr. Paul R. Wade (Department of Drug Discovery-Enterology, Johnson and Johnson Pharmaceutical) for critical reading of this manuscript and valuable advices. This research was supported by Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports Science and Technology of Japan to M. Kadowaki. (No. 14570065) and H. Kuramoto (No. 15500236).
PY - 2004/11/30
Y1 - 2004/11/30
N2 - The aim of this study was to determine the action of capsaicin in isolated rat intestine and the origin of nerve fibers expressing transient receptor potential vanilloid 1 (TRPV1: capsaicin receptor) in the rat jejunum by combination of functional and immunohistochemical experiments. Capsaicin (1 μM) produced a prolonged relaxation response (52.8±15.3% of the relaxation response to papaverine, mean±S.D., n=27) of the isolated jejunum in the presence of atropine and guanethidine. Pretreatment with the TRPV1 antagonist, capsazepine (10 μM) and ruthenium red (3 μM) significantly reduced the relaxation response to capsaicin by 78% (P<0.01) and 38% (P<0.05), respectively. Tetrodotoxin and calcitonin gene-related peptide (CGRP)-desensitization significantly reduced the response to capsaicin by 72% (P<0.01) and 42% (P<0.01), respectively. Therefore, we investigated the distribution of TRPV1-immunoreactivity (IR) in the myenteric plexus of the rat jejunum. Using antisera raised against either the N-terminal or C-terminal domains of rat TRPV1, TRPV1-IR was present in the nerve fibers, but not in the cell bodies of myenteric neurons. These TRPV1-immunoreactive nerve fibers were running in myenteric ganglia and their interconnecting strands. Most TRPV1-immunoreactive nerve fibers showed CGRP-IR, whereas few VR1-immunoreactive nerve fibers showed substance P-IR. After chronic denervation of the extrinsic nerve supply to the jejunum, both the relaxation response to capsaicin and TRPV1-immunoreactive nerve fibers completely disappeared. These findings indicate that these TRPV1-immunoreactive nerve fibers in the rat jejunum derive from extrinsic neurons and that activation of TRPV1 produces the relaxation response in the rat jejunum, at least in part, through the release of CGRP from nerve fibers expressing TRPV1.
AB - The aim of this study was to determine the action of capsaicin in isolated rat intestine and the origin of nerve fibers expressing transient receptor potential vanilloid 1 (TRPV1: capsaicin receptor) in the rat jejunum by combination of functional and immunohistochemical experiments. Capsaicin (1 μM) produced a prolonged relaxation response (52.8±15.3% of the relaxation response to papaverine, mean±S.D., n=27) of the isolated jejunum in the presence of atropine and guanethidine. Pretreatment with the TRPV1 antagonist, capsazepine (10 μM) and ruthenium red (3 μM) significantly reduced the relaxation response to capsaicin by 78% (P<0.01) and 38% (P<0.05), respectively. Tetrodotoxin and calcitonin gene-related peptide (CGRP)-desensitization significantly reduced the response to capsaicin by 72% (P<0.01) and 42% (P<0.01), respectively. Therefore, we investigated the distribution of TRPV1-immunoreactivity (IR) in the myenteric plexus of the rat jejunum. Using antisera raised against either the N-terminal or C-terminal domains of rat TRPV1, TRPV1-IR was present in the nerve fibers, but not in the cell bodies of myenteric neurons. These TRPV1-immunoreactive nerve fibers were running in myenteric ganglia and their interconnecting strands. Most TRPV1-immunoreactive nerve fibers showed CGRP-IR, whereas few VR1-immunoreactive nerve fibers showed substance P-IR. After chronic denervation of the extrinsic nerve supply to the jejunum, both the relaxation response to capsaicin and TRPV1-immunoreactive nerve fibers completely disappeared. These findings indicate that these TRPV1-immunoreactive nerve fibers in the rat jejunum derive from extrinsic neurons and that activation of TRPV1 produces the relaxation response in the rat jejunum, at least in part, through the release of CGRP from nerve fibers expressing TRPV1.
KW - CGRP
KW - Capsazepine
KW - Extrinsic denervation
KW - Relaxation response
KW - Sensory nerves
UR - http://www.scopus.com/inward/record.url?scp=8844264550&partnerID=8YFLogxK
U2 - 10.1016/j.autneu.2004.08.005
DO - 10.1016/j.autneu.2004.08.005
M3 - 学術論文
C2 - 15556833
AN - SCOPUS:8844264550
SN - 1566-0702
VL - 116
SP - 11
EP - 18
JO - Autonomic Neuroscience: Basic and Clinical
JF - Autonomic Neuroscience: Basic and Clinical
IS - 1-2
ER -