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Regulation of catecholamine biosynthetic enzymes by nitric oxide
Author(s) -
Ansell Dominique R.,
Crispo J.,
Wharton A.,
Tai T.C.
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.890.3
Subject(s) - sodium nitroprusside , tyrosine hydroxylase , protein kinase c , nitric oxide , chemistry , forskolin , medicine , endocrinology , protein kinase a , phenylethanolamine , dopamine , catecholamine , enzyme , biology , biochemistry , in vitro
The neurotransmitters/neurohormones catecholamines (CA) are involved in the sympathetic control of arterial blood pressure and cardiac function. Recent studies show that nitric oxide (NO) can regulate the release of CA from the adrenal medulla. The in vitro PC12 cell line was used to examine the effect of NO on the regulation of the CA biosynthetic enzymes: tyrosine hydroxylase (TH), dopamine‐β‐hydroxylase (DBH) and phenylethanolamine N‐methyltransferase (PNMT). Results obtained from drug treatments with the NO donor, sodium nitroprusside (SNP) constitute an assessment of its effects in PC12 cells. Treatment of cells with SNP for 6 hours significantly increased TH and PNMT mRNA levels. Combination drug studies with SNP and intracellular kinase activators (forskolin, PMA, 8‐Br‐cGMP) and inhibitors for PKA (H‐89), cGMP (6‐anilinoquinone) PKG (DT‐2) and PKC (GF109203X) were also conducted. Increases in transcript levels for TH and PNMT were obtained under combination drug treatments of SNP and activators of PKA and PKG (p<0.05). mRNA transcript levels of TH, DBH and PNMT showed significant decreases when cells were pre‐treated with PKA, PKC and PKG inhibitors. Furthermore, preliminary transfections showed activation of the PNMT promoter by SNP treatment. Results from this study suggest that NO is capable of regulating CA biosynthetic enzymes, TH and PNMT via activation of the PKA and PKG pathways.