Effects of Okadaic Acid on Rat Colon

Effects of okadaic acid (OA) on mucosal damagewere examined in rat colon. OA was sprinkled on ratcolon mucosa under observation with anelectronic-endoscopic system, and OA was also applied tothe in vivo microscopic field. The OA-induced changesin transepithelialconductance (G t ) weremeasured by the Ussing voltage clamp technique. Byendoscopic observation, the luminal sprinkling of OA (60nmol/kg) evoked transient microthrombi in the submucosalvenule, which was followed by mucosal edema.Histological study after endoscopic observation showedsubmucosal fluid retention, suggesting an increase of vascular permeability. The microthrombi werealso detected by in vivo microscopy. Byelectrophysiological study after endoscopic observationwith and without OA addition, the basal G t values were 54 ± 6.2 and 36.2 ± 4.2 mS/cm 2 ,respectively (P < 0.01). Furthermore in control rats,the serosal addition of OA evoked an increase inG t in a concentration-dependent mannerwithout increasing lactate dehydrogenase release. 2,4,6-Triaminopyrimidinium inhibitedOA-induced G t change by 60%. These resultsindicate that OA evokes an increase in paracellularpermeability of epithelium. We conclude that thedeveloped microthrombi are the first key event of OA-induced mucosaldamage, followed by an increase in permeability in thesubmucosal venule and in the paracellular pathway of theepithelium.