Segmental Heterogeneity of Epithelial Ion Transport Induced by Stimulants in Rat Distal Colon

Abstract

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...

Appearance of Segmental Discrepancy of Anion Transport in Rat Distal Colon

“…The distal colon was defined as the 7-cm-long segment proximal to the lymph node, (typically situated 3 cm away from the anus) as reported elsewhere. 9,10) The distal colon was split into four segments termed DC 1 (next to lymph node), DC 2 , DC 3 , and DC 4 , 7) respectively. Because the effect of forskolin on the segment around lymph node (DC 1 ) is very different from the other three segments and also the variation from DC 2 to DC 4 is gradually prominent, the DC 1 and DC 4 were therefore chosen to investigate the segmental discrepancy of the rat distal colonic anion transport and the possible underlying mechanism.…”

“…4) It has been reported that marked segmental heterogeneity of electrogenic Na ϩ transport or amiloride-sensive I SC (I SCamil) exists in human colon 5) and rat colon, 6) but few studies are concerned on the segmental difference of anion secretion within the distal colon. We previously have reported that the segmental heterogeneity of ion transport evoked by different stimulants in quantity such as 5-HT, ACh and forskolin existed in the rat distal colon, 7) but the ion components and the possible underlying mechanism were not clear. The aim of the present study is to further investigate the distinct effects of cAMP-dependent ion transport in different segments of rat distal colon, especially focus on the effect of luminal addition of adenylate cyclase activator, forskolin, since many biological or pathologic agents of alimentary tract cause gastrointestinal disorders by affecting the luminal environment of gastrointestinal, and also a very distal part of the rat colon is the part many colonic diseases predominated and easy to be affected or attacked under stress.…”

β-Adrenoceptors, but not dopamine receptors, mediate dopamine-induced ion transport in late distal colon of rats

“…The diverse responses in the different colonic segments can be induced by the same secretory factor (Inagaki et al 2004;Park et al 2005), and the different segments within the distal colon also manifest a segmental discrepancy (Yang et al 2006Xue et al 2007). The colorectum, a narrow part of the colon, is most vulnerable to colorectal inflammation, ulcer, polyposis, and cancer.…”

Activation of submucosal 5‐HT3 receptors elicits a somatostatin‐dependent inhibition of ion secretion in rat colon

“…The distal colon was then divided into four segments, termed DC 1 (adjacent to the lymph node), DC2, DC3 and DC4 respectively. Preliminary results indicated that the responses to 5-HT were different in the four segments (Yang et al, 2006); however, the responses in DC3 and DC4 were more reliable and consistent. Thus, DC3 and DC4 segments were used in the present study.…”

“…Although this discrepancy is hard to resolve, species and regional differences may contribute to the divergent findings on the effect of 5-HT in vitro on electrolyte transport and Isc. In our previous study, we found that even within the same species, epithelial ion transport induced by stimulants demonstrated regional heterogeneity in the rat distal colon (Yang et al, 2006). The 5-HT uptake, metabolism and neuronal systems have need noted as potential sources of variation between species and between the regions of the same species (Chetty et al, 2006).…”