Over-expression of NCS-1 in AtT-20 cells affects ACTH secretion and storage.
The effect of over-expressing neuronal calcium sensor 1 (NCS-1) upon stimulated adrenocorticotrophin (ACTH) secretion was studied in AtT-20 cells. Stably-transfected AtT-20 cell lines over-expressing NCS-1 were obtained and compared to wild type AtT-20 cells. Corticotrophin releasing factor (CRF-41)-stimulated ACTH secretion from NCS-1 over-expressing cells was significantly reduced from that obtained in wild type AtT-20 cells. The effects of other stimulants of ACTH secretion from wild type AtT-20 cells were not attenuated in NCS-1 over-expressing cells. Calcium, guanosine 5'-O-(3'-thiotriphosphate) (GTP-gamma-S) and mastoparan stimulated ACTH secretion from permeabilised wild type AtT-20 and NCS-1 over-expressing AtT-20 cells with significantly greater ACTH secretion obtained in NCS-1 over-expressing cells. This study shows that in intact cells over-expression of NCS-1 reduces exocytotic ACTH release, while in permeabilised cells increases ACTH release. NCS-1 has multiple cellular targets and that directly and indirectly via these targets acts to increase the releasable ACTH pool while inhibiting CRF-41 stimulus-secretion coupling.
Guild
S B
SB
Molecular Endocrinology Group, School of Biology, Bute Medical Building, University of St Andrews, St. Andrews KY16 9TS, UK. sbg@st-andrews.ac.uk
Murray
A T
AT
Wilson
M L
ML
Wiegand
U K
UK
Apps
D K
DK
Jin
Y
Y
Rindler
M
M
Roder
J
J
Jeromin
A
A
D000324:Adrenocorticotropic Hormone / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D036341:Intercellular Signaling Peptides and Proteins; D051379:Mice; D018613:Microscopy, Confocal; D051580:Neuronal Calcium-Sensor Proteins; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D010455:Peptides; D010903:Pituitary Gland, Anterior / Q000166:cytology*; D014162:Transfection; D014407:Tumor Cells, Cultured; D014862:Wasp Venoms / Q000494:pharmacology
D002135:Calcium-Binding Proteins; D036341:Intercellular Signaling Peptides and Proteins; D051580:Neuronal Calcium-Sensor Proteins; D009479:Neuropeptides; D010455:Peptides; D014862:Wasp Venoms; C101464:frequenin calcium sensor proteins; D016244:Guanosine 5'-O-(3-Thiotriphosphate); C037500:mastoparan; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D000242:Cyclic AMP; D002118:Calcium