Effect of microtubule network disturbance by nocodazole and docetaxel (Taxotere) on protein secretion in rat extraorbital lacrimal and parotid glands.
The role of microtubules in the exocrine secretory process is not yet well established. Contradictory effects of anti-microtubule drugs on intracellular transit and protein secretion have been reported. In this work we used microscopic techniques and pulse-chase experiments to compare the involvement of microtubules in the regulated secretory process of two rat exocrine glands: parotid and extraorbital lacrimal glands. In our experiments microtubules were either disrupted by nocodazole or stabilized by a taxoid, docetaxel (Taxotere). We show that the effect of nocodazole and docetaxel on the release of newly synthesized proteins is radically different in the two tissues; in parotid gland they only weakly affect protein release, triggered by stimulation of either muscarinic or beta-adrenergic receptors, but in lacrimal gland, they strongly inhibit protein secretion. This effect or lack of effect of the drug is independent of the signal transduction pathways involved by the different secretagogues used to trigger exocytosis. Furthermore, in lacrimal glands, studies on protein galactosylation (which occurs in the trans-Golgi compartment) indicate that postgalactosylation events are more sensitive to both drugs than pregalactosylation events. On the other hand, we show that the effect of nocodazole and docetaxel on the microtubule network is comparable on the two tissues. Finally, in lacrimal cells, we observed a scattering of the Golgi apparatus concomitant with the disruption of microtubules by nocodazole. We conclude from this study that microtubule network integrity is essential for protein secretion in lacrimal glands but not in parotid glands. This result implies that for the same physiological function, i.e. protein secretion, different mechanisms may be involved.
Robin
P
P
Laboratoire de Biochimie des Transports Cellulaires, CNRS URA 1116, Université Paris XI, Orsay/France.
Rossignol
B
B
Raymond
M N
MN
D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D004837:Epinephrine / Q000494:pharmacology; D005455:Fluorescent Antibody Technique; D005690:Galactose / Q000378:metabolism; D006023:Glycoproteins / Q000378:metabolism*; D007545:Isoproterenol / Q000494:pharmacology; D007765:Lacrimal Apparatus / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D008297:Male; D008870:Microtubules / Q000187:drug effects*; D015739:Nocodazole / Q000494:pharmacology*; D017239:Paclitaxel / Q000031:analogs & derivatives* / Q000494:pharmacology; D010306:Parotid Gland / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D043823:Taxoids
D006023:Glycoproteins; D043823:Taxoids; D000077143:Docetaxel; D015240:Phorbol 12,13-Dibutyrate; D000001:Calcimycin; D003994:Bucladesine; D002217:Carbachol; D007545:Isoproterenol; D017239:Paclitaxel; D015739:Nocodazole; D005690:Galactose; D004837:Epinephrine