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Pathway to the vagus through the sensory nerve with 5HT 3 -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).
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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
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>
5HT3 release stress ? with 5HT3-receptor GI transit accelerated!! Background 2. Stress significantly increases gastorointestinal transit via the 5HT3-receptor (Miyata et al. JPET,1992 ) However, the involvement of 5HT3-receptor is not well established in way of CRF-induced acceleration of colonic transit.
However, there may be another pathway. <5HT3 > <with 5HT3-receptor> <with 5HT3-receptor> 5HT3 Background DMV 3. 5HT3 released from EC cells increase colonic transit via 5HT3-receptor through vagus. (Fukumoto et al. AJP 284 R1269-1276, 2003) <sensory nerve> <serosa> <Ach> Smooth Muscle <mucosa> ECcell
<sensory nerve> <with 5HT3-receptor> <Ach> 5HT3 Aim stress CRF DMV • Pathway to the vagus through the sensory nerve with 5HT3-receptor <serosa> <Ach> Colon activated Smooth Muscle <mucosa> ECcell
CRF block! <sensory nerve> block! <with 5HT3-receptor> <Ach> 5HT3 block! Design DMV If 5HT3-receptor antagonist inhibits high colonic transit by CRF <serosa> Colon activated <Ach> Smooth Muscle <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 90m 10m
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 90m 10m
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!?