RECOVERY OF PROTEIN SECRETION AFTER BREFELDIN-A TREATMENT OF RAT LACRIMAL GLANDS - EFFECT OF CAMP

In exocrine cells, the discharge of secretory granule contents in resp onse to extracellular stimuli has been widely documented. However, few data are available concerning the effect of these stimuli on the step s of the secretory pathway preceding protein exocytosis. To obtain mor e data on this subject, we used brefeldin A (BFA) to perturb intracell ular protein transit. When, after exposure of the lacrimal gland lobul es to 10 mu M BFA, which led to a complete dismantling of the Golgi ap paratus and fully inhibited the secretion of newly synthesized protein s, the drug concentration was lowered to 100 nM, a restoration of prot ein secretion was observed in a secretagogue-dependent manner. Secreta gogues increasing the adenosine 3',5'-cyclic monophosphate (cAMP) leve l facilitated the recovery of protein secretion and Golgi apparatus re structuring, whereas other secretagogues, involving the calcium pathwa y, did not. Furthermore, the cAMP effect was prevented by H-89, a spec ific protein kinase A inhibitor. These effects of cAMP are due to neit her BFA degradation nor BFA excretion from the cells. We conclude from these results that in rat lacrimal glands the recovery from the drama tic damage caused by BFA is promoted by a cAMP-dependent mechanism and further suggest a role of cAMP in the regulation of the Golgi structu re and/or function.