pathway to the vagus through the sensory nerve with 5ht 3 -receptor in the colon

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