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Naoya Okada Asahikawa Medical college 4th year student

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1 Naoya Okada Asahikawa Medical college 4th year student
Pathway to the vagus through the sensory nerve with 5HT3-receptor in the colon Naoya Okada Asahikawa Medical college 4th year student

2 Backgrounds stress CRF DMV Stress induces colonic transit increasing, which is mediated by CRF through vagus.( Monnikes et Al, AJP G , 1992) <serosa> <Ach> Colon activated Smooth Muscle <mucosa>

3 GI transit accelerated!!
Background 2. Stress significantly increases gastorointestinal transit via the 5HT3-receptor (Miyata et al. JPET,1992 ) stress ? 5HT3 release with 5HT3-receptor GI transit accelerated!! However, the involvement of 5HT3-receptor is not well established in way of CRF-induced acceleration of colonic transit.

4 Background DMV <with 5HT3-receptor> 5HT3 3. 5HT3 released from EC cells increase colonic transit via 5HT3-receptor through vagus. (Fukumoto et al. AJP 284 R , 2003) <sensory nerve> <with 5HT3-receptor> <5HT3 > However, there may be another pathway. <serosa> <Ach> Smooth Muscle <mucosa> ECcell

5 Aim Pathway to the vagus through the sensory nerve with 5HT3-receptor
stress CRF <sensory nerve> <with 5HT3-receptor> <Ach> 5HT3 DMV Pathway to the vagus through the sensory nerve with 5HT3-receptor <serosa> <Ach> Colon activated Smooth Muscle <mucosa> ECcell

6 Design CRF DMV <sensory nerve> <with 5HT3-receptor> <Ach> 5HT3 block! If 5HT3-receptor antagonist inhibits high colonic transit by CRF <serosa> block! Colon activated <Ach> Smooth Muscle block! <mucosa> ECcell

7 Methods 1st. Alosetron (dose:10-5 M×0.5cc) or saline intraluminal injection 2nd. CRF (dose:1μg/5μl ) intracerebraventricular injection 3rd. 51Cr intraluminal injection 4th. Sacrifice->measurement of transit Alosetron or Saline CRF 51Cr Sacrifice 10m 10m 90m

8 How to inject intraluminally
Cannulation into the ascending colon

9 Methods 1st. Alosetron (dose:10-5 M×0.5cc) or saline intraluminal injection 2nd. CRF (dose:1μg/5μl ) intracistrnal injection 3rd. 51Cr intraluminal injection 4th. Sacrifice->measurement of transit Alosetron or Saline CRF 51Cr Sacrifice 10m 10m 90m

10 Results CRF significantly increased G.C.

11 Results A pathway via 5HT3-receptor through vagus exists.

12 Results Alosetron siginificantly inhibited G.C. increase

13 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!?

14 THE END


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