Mammalian colon plays an important role in electrolytes and water balance, and exhibits significant segmental heterogeneity along its longitudinal axis.1) The mucosa of the colonic inner surface is a typical electrolyte-transporting epithelium, which is able to move large quantities of ion and water from the mucosal side to the blood side and vice versa.2) It has been reported that the net absorption of water, sodium and chloride, 3) as well as amiloride-sensitive shortcircuit current (I SC ) 4) was dominant in distal colon than that in proximal colon, and the same activators could induce various responses in the different segments of colon. 1,6) Nobles et al. reported that the distal segments of the rat colon were more sensitive to carbachol (CCh), a Ca 2ϩ pathway activator, as well as forskolin, a cAMP pathway activator 5) which provide the evidences for the segmental specificity with regard to the intracellular signaling pathway responsible for the activation of secretion. Using PCR technique, Greig et al. found that the expression of ENaC (epithelial Na ϩ channel) was different between the rat proximal colon and distal colon.
7)Recently, the segmental heterogeneity of endogenous prostaglandin was also reported to contribute to the differences in human colon secretory responses.
1)Ion transport in gastrointestinal tract is under the control of neurotransmitters and hormones.8) The distribution of various kinds of receptors is also different in both segments of distal and proximal colon. Norepinephrine produced segment-specific effects on ion transport via different kind of receptors. 9) However, most studies were undertaken to investigate the differences between the proximal and distal colon 3,10) or between the colon and rectum.11) During our study, we found that even within the rat distal colon, the responses difference to stimulants also existed in the different segments. But there are a limited number of studies performed to compare the distinction. In the present study, the segmental heterogeneity of epithelial responses to different stimulants and its possible mechanism were investigated in rat distal colon.
MATERIALS AND METHODS
SolutionsThe Ussing chamber experiments were carried out in Krebs-Henseleit solution (K-HS) contained (in mM): NaCl, 117; KCl, 4.7; MgCl 2 , 1.2; KH 2 PO 4 , 1.2; NaHCO 3 , 24.8; CaCl 2 , 2.5; glucose, 11.1. The solution was bubbled with 95% O 2 -5% CO 2 to maintain the pH of the solution at 7.4; temperature at 37°C. Tissue Preparation Animal protocols followed guidelines established by the NIH and were approved by Animal Care and Use Committee, Capital University of Medical Sciences. Adult male Sprague-Dawley rats (Laboratory Animal Services Center, Capital University of Medical Sciences) ranging in weight from 200 to 300 g had free access to standard rodent laboratory food and water until the day of the experiments. The animals were killed by cervical dislocation. The distal colon was removed and defined as the ca. 7 cmlong segment proximal to the lymph node (typically situat...