J Pharmacol Exp Ther 2016 Nov 7;359(2):340-353. Epub 2016 Sep 7.
Laboratory of Cellular and Molecular Pharmacology, Section of Neurosciences and Clinical Pharmacology, Department of Biomedical Sciences, University of Cagliari, Cagliari, Italy (M.C.O., S.D., P.O.)
Antidepressants have been shown to affect glial cell functions and intracellular signaling through mechanisms that are still not completely understood. In the present study, we provide evidence that in glial cells the lysophosphatidic acid (LPA) receptor LPA mediates antidepressant-induced growth factor receptor transactivation, ERK1/2 signaling, and protection from oxidative stress. Thus, in C6 glioma cells and rat cortical astrocytes, ERK1/2 activation induced by either amitriptyline or mianserin was antagonized by Ki16425 and VPC 12249 (S), which block LPA and LPA receptors, and by AM966, which selectively blocks LPA Cell depletion of LPA with siRNA treatment markedly reduced antidepressant- and LPA-induced ERK1/2 phosphorylation. Read More