Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01189 (beta-endorphin)
 21,003 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Regulation of ACTH secretory pathways in cultured pituitary cells. 165 7

To determine whether a low pH intracellular "sorting" step is required to route peptides into secretory granules, the effects of pH altering drugs on the biosynthesis and secretion of peptides by AtT-20 mouse corticotrope tumor cells and rat intermediate pituitary cells were examined. Doses of each drug maintaining normal protein synthesis and cell morphology, while obliterating the intracellular pH gradients detected by acridine orange fluorescence, were experimentally determined. Regions of the cell rich in secretory granules were localized by immunocytochemistry and were found to coincide with organelles with a low internal pH. Biosynthetic labeling experiments were coupled with immunoprecipitation and sodium dodecyl sulfate polyacrylamide gel analyses to examine the biosynthesis and secretion of corticotropin (ACTH(1-39], alpha-melanotropin, ACTH(18-39), beta-endorphin, gamma-melanotropin, alpha-amidated joining peptide, and the NH2-terminal region of pro-ACTH/endorphin. Chloroquine (20-40 microM) and a mixture of NH4Cl and methylamine (2-5 mM each) dissipated pH gradients but had no effect on the synthetic rate of pro-ACTH/endorphin, the extent and rate of precursor processing to smaller peptides, the rate of basal secretion of the various peptides, or the extent to which secretion of each of the peptides could be stimulated by secretagogues. Monensin (0.1-1 microM) had no discernible effect on intracellular pH gradients yet totally blocked proteolytic processing of pro-ACTH/endorphin. Thus, a monensin-blockable step occurs in peptide processing, presumably in the trans Golgi region; however, a low pH chloroquine-sensitive sorting step is not required for processing or for routing peptides to a stable storage form which can be released in response to secretagogues.
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PMID:The role of a low pH intracellular compartment in the processing, storage, and secretion of ACTH and endorphin. 283

Intracellular sources of extramitochondrial corticoidogenic cholesterol in bovine, rat and hamster adrenocortical cells were examined in vitro by comparing the species differences in the effects of various inhibitors on the adrenocorticotropic hormone (ACTH)-induced corticoidogenesis. The inhibitors were ML-236B (3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor), W-7 (N-(6-aminohexyl)-5-chloro-1-naphthalene sulfonamide; calmodulin inhibitor), dichlorvos (O,O-dimethyl-2,2-dichlorovinyl phosphate; organic phosphorylation inhibitor), chloroquine [7-chloro-4-4-diethylamino-1-methyl-butylamino) quinoline; lysosomal enzyme inhibitor) and cycloheximide (protein synthesis inhibitor). During 2 to 3 hr incubation periods, the ACTH-induced corticoidogenesis was not inhibited by ML-236B (100 microM) in the bovine and rat adrenocortical cells. In the hamster adrenocortical cells, ML-236B (100 microM) did not affect the ACTH-induced corticoidogenesis during the initial 1 hr incubation periods; but thereafter, the ACTH-induced corticoidogenesis during the subsequent 2 hr incubation periods was completely blocked by ML-236B. The ACTH-induced corticoidogenesis was inhibited by W-7 (up to 25 microM) in the bovine and rat adrenocortical cells, but this was not the case in the hamster cells. Chloroquine (up to 400 microM) inhibited the ACTH-induced corticoidogenesis in the adrenocortical cells of three different species, but the hamster adrenal cells were much more vulnerable than the bovine and rat cells. The ACTH-induced corticoidogenesis in the adrenocortical cells of three different species were equally inhibited by cycloheximide (up to 1 mM).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Sources of extramitochondrial corticoidogenic cholesterol in the adrenal cortex. 299 19

AtT-20 cells, a mouse pituitary line, externalize a viral membrane glycoprotein and the precursor of ACTH constitutively, that is, rapidly without storage or regulation. They also have a regulated pathway in which they cleave the precursor to mature hormones, ACTH and beta-endorphin, store them in secretory granules and discharge them only in the presence of a secretagogue. An analogy exists for newly synthesized lysosomal enzymes which are either delivered to the lysosome or secreted from the cell. Targeting to the lysosomes may require a low pH step, since chloroquine causes the enzymes to be secreted from the cell. Here we show that chloroquine (200 microM) also appears to block the storage of newly synthesized ACTH in secretory granules and instead diverts it to the outside of the cell via the constitutive pathway. Chloroquine has no effect on the constitutive pathway and does not block the exocytosis of pre-packaged ACTH. Thus like lysosomal enzymes, peptide hormones are not sent to their correct destinations in the presence of chloroquine, but are diverted instead to a constitutive pathway that is chloroquine-insensitive.
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PMID:Chloroquine diverts ACTH from a regulated to a constitutive secretory pathway in AtT-20 cells. 630 Jun 82