Prostaglandin- and theophylline-induced Cl secretion in rat distal colon is inhibited by microtubule inhibitors

Publisher Website
Google Scholar
Abstract
The aim of the present study was to examine the possible role of microtubules in chloride secretion by distal rat colon stimulated by prostaglandin (PGE2) and theophylline. Distal colonic tissue from male rats was mounted in Ussing chambers, and short-circuit current (Isc) was measured to assess chloride secretion. Three microtubule inhibitors, colchicine, nocodazole, and taxol, all inhibited the stimulated Isc and reduced the 60-min integrated secretory response to PGE2 and theophylline (▪Iscdt) by 39–52%, whereas the inactive colchicine analog lumicolchicine did not. Atropine and tetrodotoxin had no effect on stimulated chloride secretion. To confirm the source of Isc, unidirectional22Na+ and36Cl− fluxes were measured in tissues exposed to lumicolchicine (control) or colchicine. Control tissues absorbed both chloride [5.0 (1.1–8.6) (median and 95% confidence interval) μeq/cm2/hr] and sodium [2.8 (0.9–7.2) μeq/cm2/hr], and this net absorption was reduced by 96% and 79%, respectively, by treatment with PGE2 and theophylline due to an increase in serosal-to-mucosal chloride and sodium movement. Colchicine-treated tissues exhibited similar net basal chloride and sodium absorption that was reduced by 71% and 75%, respectively, by treatment with PGE2 and theophylline. Thus the PGE2- and theophylline-induced increase in chloride secretion was significantly reduced by colchicine (P2- and theophylline-induced changes in sodium fluxes. Furthermore, the colchinine-related changes in stimulated chloride secretion were numerically similar to colchicine-related changes in stimulated Isc. These findings indicate that microtubules are required for normal PGE2- and theophylline-induced chloride secretion in distal rat colon and suggest that induced chloride secretion may involve vesicular insertion of ion transporters into the plasma membrane or other microtubule-dependent regulatory processes.