Pathway to the vagus through the sensory nerve with 5HT 3 -receptor in the colon
description
Transcript of Pathway to the vagus through the sensory nerve with 5HT 3 -receptor in the colon
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Pathway to the vagus through the sensory nerve with 5HT3-receptor
in the colon
Naoya Okada
Asahikawa Medical college 4th year student
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Backgrounds
1. Stress induces colonic transit increasing, which is mediated by CRF through vagus.( Monnikes et Al, AJP G137-143, 1992)
DMV
SmoothMuscle
CRFstress
<serosa>
<mucosa>
<Ach>
Colon activated
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Background2. Stress significantly i
ncreases gastorointestinal transit via the 5HT3-receptor (Miyata et al. JPET,1992 )
stress ?5HT3 release
However, the involvement of 5HT3-receptor is not well established in way of CRF-induced acceleration of colonic transit.
with 5HT3-receptor
GI transit accelerated!!
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Background
3. 5HT3 released from EC cells increase colonic transit via 5HT3-receptor through vagus. (Fukumoto et al. AJP 284 R1269-1276, 2003)
DMV
ECcell
SmoothMuscle
<sensory nerve><sensory nerve>
<serosa>
<mucosa>
<Ach>
<with 5HT3-receptor>
5HT3
<with 5HT3-receptor>
<5HT3 >
However, there may be another pathway.
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Aim
• Pathway to the vagus through the sensory nerve with 5HT3-receptor
DMV
ECcell
SmoothMuscle
CRFstress
<serosa>
<mucosa>
<Ach>
Colon activated
<sensory nerve><sensory nerve>
<with 5HT3-receptor><Ach>
5HT3
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Design
If 5HT3-receptor antagonist inhibits high colonic transit by CRF
DMV
ECcell
SmoothMuscle
CRF
<serosa>
<mucosa>
<Ach>
<sensory nerve><sensory nerve>
<with 5HT3-receptor><Ach>
5HT3
Colon activated
block!
block!
block!
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Methods1st. Alosetron (dose:10-5 M×0.5cc) or saline
intraluminal injection2nd. CRF (dose:1μg/5μl ) intracerebraventricular
injection3rd. 51Cr intraluminal injection 4th. Sacrifice->measurement of transit
Alosetron orSaline
CRF 51Cr
10m 10m 90mSacrifice
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How to inject intraluminally
• Cannulation into the ascending colon
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Methods1st. Alosetron (dose:10-5 M×0.5cc) or saline intraluminal
injection2nd. CRF (dose:1μg/5μl ) intracistrnal injection3rd. 51Cr intraluminal injection 4th. Sacrifice->measurement of transit
Alosetron orSaline
CRF 51Cr
10m 10m 90mSacrifice
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Results
• CRF significantly increased G.C.
Transit
0 1 2 3 4 5 6 7 8
G.C.
CRF
Saline
(n=8)
(n=5)
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Results
A pathway via 5HT3-receptor through vagus exists.
0 2 4 6 8
transit
G.C.
stess+atropine
stress
stress+TV
stress+alosetron
Saline
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Results
• Alosetron siginificantly inhibited G.C. increase
0 2 4 6 8 10
transit
G.C.
(n=4)
(n=4)
Alosetron+CRF
Saline+CRF
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Conclusion
• Alosetron significantly inhibits the colonic transit which is activated by CRF I.C.
->sensory nerves with 5HT3-receptors mediate colonic response to CRF I.C.
There might be a pathway to the vagus through sensory nerves with 5HT3-receptors!?
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THE END