Recovery of protein secretion after brefeldin a treatment of rat
lacrimal glands : effect of cyclic amp.
Robin, Philippe, Bernard Rossignol, and Marie-No[diaeresis]elle
Raymond.
Laboratoire de Biochimie des Transports Cellulaires, CNRS URA 1116,
b[circumflex]atiment 432, Universit[acute]e Paris XI, 91 405 Orsay
Cedex, France, Tel: (1) 69 41 71 88, Fax: (1) 69 85 37 15
APStracts 3:0139C, 1996.
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
as a tool to perturb intracellular protein transit. When, after
exposure of the lacrimal gland lobules to 10?[mu]M 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 cAMP
level facilitated the recovery of protein secretion and Golgi
apparatus restructuration, 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 neither to BFA degradation nor to 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. transit
Received 17 October 1995; accepted in final form 17 April 1996.
APS Manuscript Number C632-5.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 8 May 96