title: Regulation of ACTH secretory pathways in cultured pituitary cells.
abstract: Although chloroquine, an agent that disrupts regulated protein secretion, has previously been shown to decrease the adrenocorticotropic hormone (ACTH) secretory response to adenosine 3',5'-cyclic monophosphate or corticotropin-releasing factor (CRF) in AtT-20 and rat anterior pituitary cells, respectively, it has no effect on the response to vasopressin. The present study extended experiments with chloroquine to cultured sheep anterior pituitary cells, which have a greater maximum response to vasopressin. Chloroquine (200 microM) had no effect on basal ACTH secretion or on stimulation by vasopressin. In contrast to the rat, the net response to CRF was tripled by chloroquine in ovine cells. The effect of chloroquine on the response to CRF was more effective by coexposure of cells to CRF and chloroquine than by pretreatment with chloroquine. Monensin or vinblastine did not increase the ACTH response to CRF. The results indicate ACTH release in response to vasopressin is chloroquine insensitive in this way, can be dissociated from the mechanism that responds to CRF, and would be consistent with the CRF response mechanism involving pathways that can alter the secretory pool of ACTH. When chloroquine acts to increase the response to CRF, it is likely not to act by stabilizing the CRF-receptor complex.
authors.affiliation: Prince Henry's Institute of Medical Research, South Melbourne, Victoria, Australia.
authors.forename: J
authors.initials: J
authors.lastname: Schwartz
authors.forename: S
authors.initials: S
authors.lastname: Gibson
authors.forename: A
authors.initials: A
authors.lastname: White
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000378:metabolism*; D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology; D002478:Cells, Cultured; D002738:Chloroquine / Q000494:pharmacology; D015592:Immunoradiometric Assay; D008985:Monensin / Q000494:pharmacology; D010902:Pituitary Gland / Q000166:cytology / Q000378:metabolism*; D014747:Vinblastine / Q000494:pharmacology
chemical_list: D001127:Arginine Vasopressin; D014747:Vinblastine; D002738:Chloroquine; D000324:Adrenocorticotropic Hormone; D008985:Monensin