Prostaglandin- and theophylline-induced C1 secretion in rat distal colon is inhibited by microtubule inhibitors

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 (integral of 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, unidirectional 22Na+ and 36Cl- 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) mueq/cm2/hr] and sodium [2.8 (0.9-7.2) mueq/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 (P < 0.05 by Wilcoxon rank-sum test), whereas colchicine had no effect on PGE2- and theophylline-induced changes in sodium fluxes. Furthermore, the colchicine-related changes in stimulated chloride secretion were numerically similar to colchicine-related changes in stimulated Isc.(ABSTRACT TRUNCATED AT 250 WORDS)