Reference - Detail
| RRC ID | 43501 |
|---|---|
| Author | Fujikawa H, Kanno T, Nagata T, Nishizaki T. |
| Title | The phosphodiesterase III inhibitor olprinone inhibits hippocampal glutamate release via a cGMP/PKG pathway. |
| Journal | Neurosci Lett |
| Abstract |
Olprinone, an inhibitor of cyclic nucleotide phosphodiesterase III, inhibited an increase in intracellular Ca(2+) concentrations for acutely dissociated rat hippocampal pyramidal neurons induced by extracellular high K(+) (35 mM) depolarization. Olprinone (100 microM) significantly reduced spontaneous glutamate release from rat hippocampal slices. Furthermore, olprinone significantly decreased the rate of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor-mediated miniature excitatory postsynaptic currents (AMPA-mEPSCs) monitored from CA1 pyramidal neurons of rat hippocampal slices, and the effect was blocked by KT5823, an inhibitor of protein kinase G (PKG), but not by H-89, an inhibitor of protein kinase A (PKA). In the PKA assay using PC-12 cells, olprinone did not activate PKA. Taken together, the results of the present study show that olprinone attenuates intracellular Ca(2+) rise through voltage-sensitive Ca(2+) channels and inhibits presynaptic glutamate release via a cGMP/PKG pathway. |
| Volume | 448(2) |
| Pages | 208-11 |
| Published | 2008-12-26 |
| DOI | 10.1016/j.neulet.2008.10.079 |
| PII | S0304-3940(08)01490-0 |
| PMID | 18983890 |
| MeSH | Animals Calcium / metabolism Carbazoles / pharmacology Cyclic GMP / metabolism* Cyclic GMP-Dependent Protein Kinases / antagonists & inhibitors Cyclic GMP-Dependent Protein Kinases / metabolism* Excitatory Postsynaptic Potentials / drug effects Glutamic Acid / metabolism* Hippocampus / drug effects* Hippocampus / metabolism Imidazoles / pharmacology* In Vitro Techniques Isoquinolines / pharmacology Male Membrane Potentials / physiology Phosphodiesterase 3 Inhibitors Phosphodiesterase Inhibitors / pharmacology* Potassium / metabolism Protein Kinase Inhibitors / pharmacology Pyramidal Cells / drug effects Pyramidal Cells / metabolism Pyridones / pharmacology* Rats Rats, Wistar Receptors, AMPA / metabolism Signal Transduction* / drug effects Sulfonamides / pharmacology |
| IF | 2.274 |
| Times Cited | 9 |
| WOS Category | NEUROSCIENCES |
| Resource | |
| Human and Animal Cells | PC-12(RCB0009) |