Anion secretion in mammalian distal colon plays an important role in body electrolyte and water balance under physiological and pathophysiological conditions. Electrogenic Cl Ϫ secretion is the fundamental means of intestinal mucosal surface hydration as a primitive defense mechanism which can prevent the mucosa from noxious stimuli, and several human diseases including secretory diarrhea and cystic fibrosis result from its defective regulation.2) HCO 3 Ϫ , similar to Cl Ϫ , is not only an important component of normal colonic fluid, contributing to the maintenance and regulation of the pH microclimate observed at the luminal surface of the colon, but also a major participator of the secreted fluid in a couple of diarrhea diseases.3) Moreover, HCO 3 Ϫ in feces is significantly reduced in patients with active ulcerative colitis, possibly due to the mucosa inflammation-induced impairment of the colonic anion exchange. 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.
8) MATERIALS AND METHODS
Preparation of Colonic MucosaAnimal protocols followed guidelines established by the NIH and were approved by Animal Care and Use Committee, Capital Medical University. Adult male Sprague-Dawley rats (Laboratory Animal Services Center, Capital Medical University) ranging in weight from 200 to 300 g fed with a standard rat diet and tap water, were killed by cervical dislocation, and a segment of distal colon of approximately ca. 7 cm in length was removed, rinsed with ice-cold Krebs-Henseleit solution (KHS). 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 t...