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Rho Kinase Inhibitor Y‐27632 Down‐Regulates Norepinephrine Synthesis and Release in PC12 Cells
Author(s) -
Duan WeiGang,
Shang Jing,
Jiang ZhenZhou,
Yao JinCheng,
Yun Yu,
Yan Ming,
Shu Bin,
Lin Qing,
Yu ZePu,
Zhang LuYong
Publication year - 2009
Publication title -
basic and clinical pharmacology and toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.805
H-Index - 90
eISSN - 1742-7843
pISSN - 1742-7835
DOI - 10.1111/j.1742-7843.2008.00314.x
Subject(s) - norepinephrine , neurite , tyrosine hydroxylase , neurotransmitter , synapsin , synapsin i , protein kinase a , chemistry , kinase , rho associated protein kinase , acetylcholine , endocrinology , medicine , biology , microbiology and biotechnology , dopamine , biochemistry , receptor , synaptic vesicle , in vitro , vesicle , membrane
Rho kinase inhibition is beneficial for neurite outgrowth and nerve disorders, and the Rho kinase inhibitors have been regarded as promising agents to treat neural diseases. The main aim of the study was to elucidate how Rho kinase inhibitor Y‐27632 regulates neurotransmitter norepinephrine synthesis and release in PC12 cells when neurite outgrowth was induced. PC12 cells were treated with Y‐27632 for 6 days. The amount of norepinephrine synthesized in PC12 cells and the amount released evoked by acetylcholine or by KCl were determined by norepinephrine enzyme‐linked immunosorbent assay kits. The results showed that the amount of norepinephrine both synthesized and released was down‐regulated with a concentration‐dependent relationship. Further results of Western blotting found that the protein expression of tyrosine hydroxylase and synapsin I (especially its active form, synapsin I phosphoSer603) was also down‐regulated, which were directly related to synthesis and release of norepinephrine, respectively. All the results suggest that Y‐27632 is able to down‐regulate norepinephrine synthesis and release, the direct mechanism of which may be associated with down‐regulation on expression of some proteins, including tyrosine hydroxylase and synapsin I.