Blockade of the classical pathway of protein secretion does not affect the cellular exportation of lipocortin 1

The mechanism by which lipocortin 1 (LC1) is extruded from cells in the brain and periphery in response to a glucocorticoid challenge is unknown. This study examined the influence of three inhibitors of the classical endoplasmic reticulum-Golgi pathway of protein secretion on the dexamethasone-induced (0.1 mu M, 2-3 h) cellular exportation of LC1 in vitro in brain (cortex, hippocampus, hypothalamus), anterior pituitary tissue and peritoneal macrophages. In all instances, the steroid-induced exportation of LC1 was unaffected by brefeldin A (1.4 mu M), monensin (10 mu M) and nocodazole (3.3 mu M); however, these drugs readily blocked the release of corticotrophin from pituitary tissue. These data suggest that LC1 is exported by a mechanism distinct from the classical pathway of protein secretion. (C) 1998 Elsevier Science B.V.