Submitted on December 8, 2006
Accepted on March 31, 2007
Luminally released serotonin stimulates colonic motility and accelerates colonic transit in rats
Kiyoshi Tsukamoto1, Hajime Ariga1, Christopher Mantyh1, Theodore N. Pappas2, Hidenori Yanagi3, Takehira Yamamura3, and Toku Takahashi2*
1 surgery, Duke university, durham, North Carolina, United States
2 Department of Surgery, Duke University Medical Center, Durham,, North Carolina, United States
3 Second Department of Surgery, Hyogo College of Medicine, Japan
* To whom correspondence should be addressed. E-mail: ttakahas{at}duke.edu.
Enterochromaffin (EC) cells of the epithelial cells release 5-HT into the lumen as well as basolateral border. However, the physiological role of released 5-HT into the lumen is poorly understood. Concentrations of 5-HT in the colonic mucosa, colonic lumen and feces were measured by HPLC in rats. To investigate whether intraluminal 5-HT accelerates colonic transit, 5-HT and 51Cr were administered into the lumen of the proximal colon, and colonic transit was measured. To investigate whether 5-HT is released into the lumen, we utilized ex vivo model of isolated vascularly and luminally perfused rat proximal colon. To investigate whether luminal 5-HT is involved in regulating stress-induced colonic motility, the distal colonic motility was recorded under the stress-loading and a 5-HT3 receptor antagonist (ondansetron, 10-6 M, 0.5 ml) was administered intraluminally of the distal colon. Tissue content of 5-HT in the proximal colon (15.2 ± 4.3 ng/mg wet tissue) was significantly higher than that in the distal colon (3.3 ±0.7 ng/mg wet tissue), while fecal content and luminal concentration of 5-HT was almost the same between the proximal and distal colon. Luminal administration of 5-HT (10-6-10-5 M) significantly accelerated colonic transit. Elevation of intraluminal pressure by10 cmH2O significantly increased the luminal concentration of 5-HT, but not vascular concentration of 5-HT. Stress-induced stimulation of the distal colonic motility was significantly attenuated by the luminal administration of ondansetron. These results suggest that luminally released 5-HT from EC cells plays an important role to regulate colonic motility in rats.
