Metabotropic glutamate receptor involvement in phosphoinositide hydrolysis stimulation by an endogenous Na+, K+-ATPase inhibitor and ouabain in neonatal rat brain
| Autor: | M.A Calviño, G. Rodríguez de Lores Arnaiz, Clara Peña |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
Male
medicine.medical_specialty Receptor Metabotropic Glutamate 5 Muscarinic Antagonists Pharmacology Biology Phosphatidylinositols Receptors Metabotropic Glutamate Ouabain chemistry.chemical_compound Developmental Neuroscience Internal medicine medicine Animals Enzyme Inhibitors Rats Wistar Cerebral Cortex Metabotropic glutamate receptor 5 Hydrolysis Glutamate receptor Brain Rats Dizocilpine Endocrinology Animals Newborn chemistry Competitive antagonist Metabotropic glutamate receptor CNQX Metabotropic glutamate receptor 1 Female Indicators and Reagents Sodium-Potassium-Exchanging ATPase Inositol Cadmium Developmental Biology medicine.drug |
| Zdroj: | Developmental Brain Research. 138:167-175 |
| ISSN: | 0165-3806 |
| DOI: | 10.1016/s0165-3806(02)00469-8 |
| Popis: | The mechanism of action of an endogenous Na(+), K(+)-ATPase inhibitor, termed endobain E, on phosphoinositide hydrolysis was studied in neonatal rat brain cortex and compared with that of ouabain. Lack of additivity for endobain E and glutamate paired stimulation on inositol phosphates accumulation suggested that they share at least a common step on inositol phosphate metabolism, as previously advanced for ouabain. In addition, Cd(2+) sensitivity of endobain E and ouabain effects strengthened the involvement of glutamate receptors. The participation of ionotropic glutamate receptors on endobain E- and ouabain-induced phosphoinositide hydrolysis seems untenable, since antagonists dizocilpine and CNQX proved unable to inhibit these effects. However, the endobain E effect was blocked by 2 x 10 (-4) M L-AP3 (an antagonist for group I mGluRs) when at least a 15-min preincubation protocol was employed. Maximal inhibition of endobain E effect (42%) occurred when L-AP3 preincubation was extended to 60 min, as already shown with glutamate, but only a trend to decrease was recorded with ouabain. At variance, the ouabain effect was reduced to 50% employing 5 x 10 (-4) M MCPG (a competitive antagonist for group I mGluRs), whereas no blockade was observed with endobain E or glutamate. In addition, MPEP (a selective mGluR5 antagonist) partially reduced ouabain, endobain E and glutamate responses and the selective mGluR1 antagonist LY367385 showed no activity at all. To sum up, the present findings support the involvement of mGluR5 in both endobain E and ouabain phosphoinositide hydrolysis stimulation in neonatal rat brain, in spite of dissimilar response to tested antagonists. |
| Databáze: | OpenAIRE |
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