Dataset Information
Antidepressant amitriptyline-induced matrix metalloproteinase-9 activation is mediated by Src family tyrosine kinase, which leads to glial cell line-derived neurotrophic factor mRNA expression in rat astroglial cells.
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ABSTRACT:
Methods and results: Treatment of rat C6 astroglial cells (C6 cells) with amitriptyline increased Src family tyrosine kinase phosphorylation in a time and concentration-dependent manner. Amitriptyline-induced GDNF mRNA expression was blocked by Src family tyrosine kinase inhibitors. In addition, inhibiting Src family tyrosine kinase blocked amitriptyline-induced zymographic MMP-9 activation in C6 cells. The amitriptyline-induced zymographic MMP-9 activity was completely blocked by selective inhibition of G?i/o protein and LPAR1. Furthermore, the amitriptyline-induced Src family tyrosine kinase phosphorylation was blocked by LPAR1, but not MMP-9 inhibition, indicating that Src family tyrosine kinase involvement is downstream of LPAR1.
Conclusions: The current findings suggest that the pharmacological effect of antidepressant such as amitriptyline is mediated through an intracellular signaling pathway via the LPAR1/G?i/o /Src family tyrosine kinase, which leads to MMP-9 activation and GDNF production.
SUBMITTER: Abe H
PROVIDER: S-EPMC7292280 | biostudies-literature | 2019 Sep
REPOSITORIES: biostudies-literature
Publications
Antidepressant amitriptyline-induced matrix metalloproteinase-9 activation is mediated by Src family tyrosine kinase, which leads to glial cell line-derived neurotrophic factor mRNA expression in rat astroglial cells.
Neuropsychopharmacology reports 20190425 3
<h4>Background</h4>Astrocytes have been implicated in the pathophysiology of mood disorders and in the mechanism of the pharmacological effects of antidepressant drugs by the production of neurotrophic/growth factors. Previous studies have identified astrocyte-expressed Gα<sub>i/o</sub> -coupled lysophosphatidic acid receptor 1 (LPAR1), as being involved in antidepressant-induced production of glial cell line-derived neurotrophic factor (GDNF) and matrix metalloproteinase-9 (MMP-9) activation, a ...[more]
