Non-specific effects of the MEK inhibitors PD098,059 and U0126 (cas 109511-58-2) on glutamate release from hippocampal synaptosomes
-
Add time:07/26/2019 Source:sciencedirect.com
In order to investigate a role for the extracellular-signal-regulated kinases 1 and 2 (ERK1/2) on hippocampal neurotransmitter release, we studied the effect of commonly used MEK (mitogen-activated protein kinase [MAPK]/ERK kinase) inhibitors, PD098,059 and U0126 (cas 109511-58-2), on depolarization-induced glutamate release. PD098,059 inhibited glutamate release from hippocampal synaptosomes stimulated with 15 mM KCl in a concentration-dependent manner. At the same range of concentrations, PD098,059 inhibited basal and KCl-stimulated ERK1/2 phosphorylation. U0126, however, did not significantly affect KCl-evoked glutamate release at concentrations shown to inhibit ERK activity. Nonetheless, U0126 unspecifically potentiated depolarization-induced Ca2+-independent glutamate release, which masked a small dose-dependent inhibitory effect on the Ca2+-dependent release. PD098,059 reduced the [Ca2+]i response to KCl by partially inhibiting Ca2+ entry through N- and P-/Q-type voltage-gated Ca2+ channels, whereas U0126 did not affect depolarization-induced Ca2+ influx. To overcome the unspecific effect of PD098,059 on Ca2+ entry, we studied the effect of both MEK inhibitors on glutamate release stimulated by a Ca2+ ionophore. PD098,029 and U0126 showed a small dose-dependent inhibitory effect on ionomycin-induced glutamate release, at concentrations shown to inhibit ionomycin-stimulated ERK phosphorylation. These findings uncover new unspecific actions for both MEK inhibitors and suggest a minor role for ERK in modulating glutamate release in the hippocampus.
We also recommend Trading Suppliers and Manufacturers of U0126 (cas 109511-58-2). Pls Click Website Link as below: cas 109511-58-2 suppliers
Prev:Prevention of LLC-PK1 cell overgrowth in a bioartificial renal tubule device using a MEK inhibitor, U0126 (cas 109511-58-2)
Next:Using U0126 (cas 109511-58-2) to dissect the role of the extracellular signal-regulated kinase 1/2 (ERK1/2) cascade in the regulation of gene expression by endothelin-1 in cardiac myocytes) - 【Back】【Close 】【Print】【Add to favorite 】
- Related Information
- MEK inhibitors: The chemistry and biological activity of U0126 (cas 109511-58-2), its analogs, and cyclization products07/28/2019
- Using U0126 (cas 109511-58-2) to dissect the role of the extracellular signal-regulated kinase 1/2 (ERK1/2) cascade in the regulation of gene expression by endothelin-1 in cardiac myocytes07/27/2019
- Prevention of LLC-PK1 cell overgrowth in a bioartificial renal tubule device using a MEK inhibitor, U0126 (cas 109511-58-2)07/25/2019
- Nociceptin and its metabolite attenuate U0126 (cas 109511-58-2)-induced memory impairment through a nociceptin opioid peptide (NOP) receptor-independent mechanism07/24/2019
- Effects of MEK-Specific Inhibitor U0126 (cas 109511-58-2) on the Conidial Germination, Appressorium Production, and Pathogenicity of Setosphaeria turcica07/23/2019
- Quantitative NMR analysis of Erk activity and inhibition by U0126 (cas 109511-58-2) in a panel of patient-derived colorectal cancer cell lines07/22/2019
- Antiviral activity of the MEK-inhibitor U0126 (cas 109511-58-2) against pandemic H1N1v and highly pathogenic avian influenza virus in vitro and in vivo07/20/2019
- mTOR inhibitor temsirolimus and MEK1/2 inhibitor U0126 (cas 109511-58-2) promote chromosomal instability and cell type-dependent phenotype changes of glioblastoma cells07/21/2019
- U0126 (cas 109511-58-2) attenuates ischemia/reperfusion-induced apoptosis and autophagy in myocardium through MEK/ERK/EGR-1 pathway07/19/2019