Pathway to the vagus through the sensory nerve with 5HT3-receptor
in the colon
Naoya Okada
Asahikawa Medical college 4th year student
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
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!!
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.
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
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!
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
How to inject intraluminally
• Cannulation into the ascending colon
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
Results
• CRF significantly increased G.C.
Transit
0 1 2 3 4 5 6 7 8
G.C.
CRF
Saline
(n=8)
(n=5)
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
Results
• Alosetron siginificantly inhibited G.C. increase
0 2 4 6 8 10
transit
G.C.
(n=4)
(n=4)
Alosetron+CRF
Saline+CRF
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!?
THE END
