The role of microtubules in the exocrine secretory process is not yet
well established, and their disruption by anti-microtubule drugs leads
to variable effects on intracellular transit and protein secretion. W
e investigated the involvement of microtubules in the regulated secret
ory process of rat parotid glands using microscopic techniques and pul
se-chase experiments. We showed that 10 mu M colchicine or nocodazole
destroys the microtubule network in parotid acinar cells but only weak
ly reduces the release of newly synthesized proteins. The half-effect
was obtained with 0.22 mu M colchicine. Moreover, this small reduction
was found to be independent of the nature of the drug (colchicine, co
lcemid, or nocodazole) and of the nature of the stimulation (beta-adre
nergic or cholinergic pathways). Using nocodazole, we have been able t
o determine that the steps affected by the drug are very early events
in the secretory pathway. Finally, we showed by kinetic analysis that
microtubule disruption slows protein release only moderately but does
not reduce the total amount of secreted protein. We conclude from this
study that microtubule integrity is not essential for protein secreti
on in rat parotid gland. (C) 1994 Wiley-Liss, Inc.