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 stimul ated adrenocorticotrophin (ACTH) secretion was studied in AtT-20 cells. Sta bly-transfected AtT-20 cell lines over-expressing NCS-1 were obtained and c ompared to wild type AtT-20 cells. Corticotrophin releasing factor (CRF-41) -stimulated ACTH secretion from NCS-1 over-expressing cells was significant ly reduced from that obtained in wild type AtT-20 cells. The effects of oth er stimulants of ACTH secretion from wild type AtT-20 cells were not attenu ated in NCS-I over-expressing cells. Calcium, guanosine 5'-O-(3'-thiotripho sphate) (GTP-gamma -S) and mastoparan stimulated ACTH secretion from permea bilised wild type AtT-20 and NCS-I over-expressing AtT-20 cells with signif icantly greater ACTH secretion obtained in NCS-I over-expressing cells. Thi s study shows that in intact cells over-expression of NCS-I reduces exocyto tic 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 s timulus-secretion coupling. (C) 2001 Elsevier Science Ireland Ltd. All righ ts reserved.