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 response to extracellular stimuli has been widely documented. However, few data are available concerning the effect of these stimuli on the steps of the secretory pathway preceding protein exocytosis. To obtain more data on this subject, we used brefeldin A (BFA) to perturb intracellular protein transit. When, after exposure of the lacrimal gland lobules to 10 microM BFA, which led to a complete dismantling of the Golgi apparatus and fully inhibited the secretion of newly synthesized proteins, the drug concentration was lowered to 100 nM, a restoration of protein secretion was observed in a secretagogue-dependent manner. Secretagogues increasing the adenosine 3',5'-cyclic monophosphate (cAMP) level facilitated the recovery of protein secretion and Golgi apparatus restructuring, whereas other secretagogues, involving the calcium pathway, did not. Furthermore, the cAMP effect was prevented by H-89, a specific protein kinase A inhibitor. These effects of cAMP are due to neither BFA degradation nor BFA excretion from the cells. We conclude from these results that in rat lacrimal glands the recovery from the dramatic damage caused by BFA is promoted by a cAMP-dependent mechanism and further suggest a role of cAMP in the regulation of the Golgi structure and/or function.
Robin
P
P
Laboratoire de Biochimie des Transports Cellulaires, Université Paris XI, Orsay, France.
Rossignol
B
B
Raymond
M N
MN
D000818:Animals; D020126:Brefeldin A; D000242:Cyclic AMP / Q000378:metabolism*; D003517:Cyclopentanes / Q000494:pharmacology*; D005089:Exocytosis / Q000187:drug effects*; D006056:Golgi Apparatus / Q000378:metabolism; D007765:Lacrimal Apparatus / Q000378:metabolism* / Q000648:ultrastructure; D008297:Male; D014176:Protein Biosynthesis; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D003517:Cyclopentanes; D011500:Protein Synthesis Inhibitors; D020126:Brefeldin A; D000242:Cyclic AMP