EFFECT OF MICROTUBULE NETWORK DISTURBANCE BY NOCODAZOLE AND DOCETAXEL(TAXOTERE(R)) 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 i ntracellular transit and protein secretion have been reported. In this work we used microscopic techniques and pulse-chase experiments to co mpare the involvement of microtubules in the regulated secretory proce ss of two rat exocrine glands: parotid and extraorbital lacrimal gland s, In our experiments microtubules were either disrupted by nocodazole or stabilized by a taxoid, docetaxel (Taxotere(R)). 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 e ither 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 involv ed by the different secretagogues used to trigger exocytosis. Furtherm ore, in lacrimal glands, studies on protein galactosylation (which occ urs 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 docetax el on the microtubule network is comparable on the two tissues, Finall y, in lacrimal cells, we observed a scattering of the Golgi apparatus concomitant with the disruption of microtubules by nocodazole. We conc lude from this study that microtubule network integrity is essential f or protein secretion in lacrimal glands but not in parotid glands, Thi s result implies that for the same physiological function, i.e. protei n secretion, different mechanisms may be involved.