Over-expression of NCS-1 in AtT-20 cells affects ACTH secretion and storage

The effect of over-expressing neuronal calcium sensor I (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-I 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-I over-expressing AtT-20 cells with significantly greater ACTH secretion obtained in NCS-I over-expressing cells. This study shows that in intact cells over-expression of NCS-I reduces exocytotic ACTH release, while in permeabilised cells increases ACTH release. NCS-I 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. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.