Changes of dopamine content and cell proliferation by dexamethsone via pituitary adenylate cyclase-activating polypeptide in PC12 cell

Abstract

Pituitary adenylate cyclase-activating polypeptide (PACAP) is an endogenous neuropeptide observed in adrenal gland and sympathetic ganglia to regulate catecholamine synthesis and release. Both PACAP and glucocorticoid showed the activity to elevate catecholamine level through the stimulation of biosynthesis. However, the relationship of glucocorticoid and PACAP for this action is still unclear. Thus, alterations of gene expression, dopamine (DA) content, and cell proliferation in rat pheochromocytoma PC12 cells are employed as indicators to clarify this relationship in the present study. From the analysis of RT-PCR, the mRNA level of PACAP was observed to be raised by dexamethasone (DEX) and this action was blocked in cells treated with RU486 (mifepristone), a glucocorticoid receptor (GR) antagonist, or actinomycin D, a transcriptional inhibitor. An increase of DA content by HPLC analysis and/or cell proliferation identified by MTT assay by DEX was also observed which could be inhibited by PACAP (6-38) at concentration sufficient to block PACAP type 1 (PAC1) receptor. These results suggest that PACAP is involved in DEX-induced DA biosynthesis and cell proliferation in PC12 cells.