Naoya Okada Asahikawa Medical college 4th year student

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Presentation transcript:

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

Backgrounds stress CRF DMV Stress induces colonic transit increasing, which is mediated by CRF through vagus.( Monnikes et Al, AJP G137-143, 1992) <serosa> <Ach> Colon activated Smooth Muscle <mucosa>

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.

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 R1269-1276, 2003) <sensory nerve> <with 5HT3-receptor> <5HT3 > However, there may be another pathway. <serosa> <Ach> Smooth Muscle <mucosa> ECcell

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

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

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

How to inject intraluminally Cannulation into the ascending colon

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

Results CRF significantly increased G.C.

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

Results Alosetron siginificantly inhibited G.C. increase

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