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 microM, 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 microM), monensin (10 microM) and nocodazole (3.3 microM); 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.
Philip
J G
JG
Department of Neuroendocrinology, Imperial College School of Medicine, Charing Cross Hospital, London, UK.
Flower
R J
RJ
Buckingham
J C
JC
D000818:Animals; D017305:Annexin A1 / Q000378:metabolism*; D001692:Biological Transport; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D020126:Brefeldin A; D003517:Cyclopentanes / Q000494:pharmacology; D003907:Dexamethasone / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008985:Monensin / Q000494:pharmacology; D015739:Nocodazole / Q000494:pharmacology; D010903:Pituitary Gland, Anterior / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D017305:Annexin A1; D003517:Cyclopentanes; D020126:Brefeldin A; D003907:Dexamethasone; D008985:Monensin; D015739:Nocodazole