Segmental heterogeneity of epithelial ion transport induced by stimulants in rat distal colon

Abstract

Mammalian colon plays an important role in electrolyte and water balance, and exhibits significant segmental heterogeneity. The different responses to stimulants even exist in different segments of rat distal colon. The present study focus on the segmental heterogeneity of epithelial responses to different stimulants and investigates the possible mechanism by using short circuit current recording technique. Baseline ISC in the segment 4 of distal colon (DC4, 20.8±2.8 μA·cm-2) was significantly lower than that in the segment 1 of distal colon (DC1, 40.5±1.9 μA·cm-2). Basolateral application of indomethacin induced a larger reduction of the baseline ISC in DC4 (-28.2±3.9 μA·cm-2) than that in DC1 (-10.1±3.9 μA·cm-2). Moreover DC 4 are more sensitive to foskolin (a cAMP activator, apical side), Ach (basolateral side) and 5-HT (basolateral side) than DC1, which was not affected by pretreatment with amiloride, a blocker of epithelial Na + channel. Basolateral pretreatment with atropine (muscarinic cholinergic receptor antagonist) for 10 min, Ach-induced ΔISC increases in both DC1 and DC4 were totally blocked. Otherwise, 5-HT4 receptor antagonist GR113808 (basolateral side) and SB-204070 (basolateral side) completely inhibited 5-HT-induced ISC increases in both DC1 and DC4. Taken together, the results suggested that the segmental heterogeneity of epithelial responses to different stimulants exists in rat distal colon. And it is more likely related to the dissimilar distribution of membrane proteins involved in the ion transports within different segments of rat distal colon. © 2006 Pharmaceutical Society of Japan.