Inhibition of glycoconjugate secretion by colchicine and cytochalasin B. An in vitro study of human airway.

Abstract

The effects have been analyzed of cytochalasin B and colchicine on the secretion of glycoconjugates by human bronchial explants labeled in vitro with radioactive glucosamine. Both cytochalasin B and colchicine had no effect on baseline 14C-labeled glycoconjugate release but caused a dose-dependent (10(-7)-10(-4) M) inhibition of 14C-glycoconjugate release and discharge of labeled macromolecules from mucous and serous cells induced by 5 X 10(-5) M methacholine. Quantitative autoradiographic analyses showed that neither cytochalasin B nor colchicine inhibited 3H-threonine or 3H-glucosamine incorporation into mucous and serous cells of the submucosal glands or goblet cells of the airway epithelium. Colchicine (10(-5) M) but not cytochalasin B significantly reduced the rate at which labeled macromolecules were transported through mucous, serous and goblet cells but this effect was not observed until 4h after the addition of colchicine. Neither cytochalasin B nor colchicine affected the basal rate of labeled-macromolecule discharge from mucous, serous or goblet cells. At a concentration of 10(-5) M, both agents completely inhibited the increase in labeled-macromolecule discharge induced in mucous and serous cells by methacholine. Our results suggest that in the submucosal gland of human airways microtubules and microfilaments may be important in secretagogue-induced but not in baseline cellular glycoconjugate discharge, implying that the mechanisms of the two processes differ significantly. Furthermore, a role for microtubules is suggested in the transport of secretory granules through mucous, serous and goblet cells.