PMID- 16990446
OWN - NLM
STAT- MEDLINE
DCOM- 20070322
LR  - 20220311
IS  - 0193-1857 (Print)
IS  - 0193-1857 (Linking)
VI  - 292
IP  - 1
DP  - 2007 Jan
TI  - 5-Hydroxytryptophan activates colonic myenteric neurons and propulsive motor 
      function through 5-HT4 receptors in conscious mice.
PG  - G419-28
AB  - Serotonin [5-hydroxytryptamine (5-HT)] acts as a modulator of colonic motility 
      and secretion. We characterized the action of the 5-HT precursor 
      5-hydroxytryptophan (5-HTP) on colonic myenteric neurons and propulsive motor 
      activity in conscious mice. Fos immunoreactivity (IR), used as a marker of 
      neuronal activation, was monitored in longitudinal muscle/myenteric plexus whole 
      mount preparations of the distal colon 90 min after an intraperitoneal injection 
      of 5-HTP. Double staining of Fos IR with peripheral choline acetyltransferase 
      (pChAT) IR or NADPH-diaphorase activity was performed. The injection of 5-HTP 
      (0.5, 1, 5, or 10 mg/kg ip) increased fecal pellet output and fluid content in a 
      dose-related manner, with a peak response observed within the first 15 min 
      postinjection. 5-HTP (0.5-10 mg/kg) dose dependently increased Fos expression in 
      myenteric neurons, with a maximal response of 9.9 +/- 1.0 cells/ganglion [P < 
      0.05 vs. vehicle-treated mice (2.3 +/- 0.6 cells/ganglion)]. There was a positive 
      correlation between Fos expression and fecal output. Of Fos-positive ganglionic 
      cells, 40 +/- 4% were also pChAT positive and 21 +/- 5% were NADPH-diaphorase 
      positive in response to 5-HTP, respectively. 5-HTP-induced defecation and Fos 
      expression were completely prevented by pretreatment with the selective 5-HT4 
      antagonist RS-39604. These results show that 5-HTP injected peripherally 
      increases Fos expression in different populations of cholinergic and nitrergic 
      myenteric neurons in the distal colon and stimulates propulsive colonic motor 
      function through 5-HT4 receptors in conscious mice. These findings suggest an 
      important role of activation of colonic myenteric neurons in the 5-HT4 
      receptor-mediated colonic propulsive motor response.
FAU - Wang, L
AU  - Wang L
AD  - Digestive Diseases Research Center and Center for Neurovisceral Sciences and 
      Woman's Health, Division of Digestive Diseases, Department of Medicine, David 
      Geffen School of Medicine, University of California, Los Angeles, USA. 
      lixinw@ucla.edu
FAU - Martinez, V
AU  - Martinez V
FAU - Kimura, H
AU  - Kimura H
FAU - Tache, Y
AU  - Tache Y
LA  - eng
GR  - DK-41301/DK/NIDDK NIH HHS/United States
GR  - P50-DK-64539/DK/NIDDK NIH HHS/United States
GR  - R01-DK-57238/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20060921
PL  - United States
TA  - Am J Physiol Gastrointest Liver Physiol
JT  - American journal of physiology. Gastrointestinal and liver physiology
JID - 100901227
RN  - 158165-40-3 (Receptors, Serotonin, 5-HT4)
RN  - C1LJO185Q9 (5-Hydroxytryptophan)
RN  - EC 1.6.99.1 (NADPH Dehydrogenase)
RN  - EC 2.3.1.6 (Choline O-Acetyltransferase)
SB  - IM
MH  - 5-Hydroxytryptophan/*pharmacology
MH  - Animals
MH  - Choline O-Acetyltransferase/metabolism
MH  - Colon/*innervation
MH  - Defecation/drug effects/physiology
MH  - Mice
MH  - Motor Activity/drug effects/physiology
MH  - Myenteric Plexus/drug effects/*physiology
MH  - NADPH Dehydrogenase/metabolism
MH  - Neurons/drug effects/*physiology
MH  - Receptors, Serotonin, 5-HT4/drug effects/*physiology
EDAT- 2006/09/23 09:00
MHDA- 2007/03/23 09:00
CRDT- 2006/09/23 09:00
PHST- 2006/09/23 09:00 [pubmed]
PHST- 2007/03/23 09:00 [medline]
PHST- 2006/09/23 09:00 [entrez]
AID - 00289.2006 [pii]
AID - 10.1152/ajpgi.00289.2006 [doi]
PST - ppublish
SO  - Am J Physiol Gastrointest Liver Physiol. 2007 Jan;292(1):G419-28. doi: 
      10.1152/ajpgi.00289.2006. Epub 2006 Sep 21.