Multiple pathways for regulation of the KCl-induced [3H]-GABA release by metabotropic glutamate receptors, in primary rat cortical cultures
| Autor: | Hervé Schaffhauser, John A. Kemp, John Richard Pink, Vincent Mutel, Zaiga Bleuel, J. G. Richards, Fabienne Goepfert, Jayne Cartmell, Frédéric Knoflach, Geo Adam |
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| Rok vydání: | 1998 |
| Předmět: |
medicine.medical_specialty
Patch-Clamp Techniques Blotting Western chemistry.chemical_element Calcium Biology Receptors Metabotropic Glutamate Tritium Potassium Chloride chemistry.chemical_compound Internal medicine medicine Cyclic AMP Animals Receptor Neurotransmitter Molecular Biology Cells Cultured In Situ Hybridization gamma-Aminobutyric Acid Cerebral Cortex General Neuroscience Calcium channel Glutamate receptor Antagonist Rats Inbred Strains Rats Endocrinology Metabotropic receptor chemistry Metabotropic glutamate receptor Biophysics Neurology (clinical) Developmental Biology |
| Zdroj: | Brain research. 782(1-2) |
| ISSN: | 0006-8993 |
| Popis: | In rat cortical primary cultures, group II- and III-metabotropic glutamate receptor-selective agonists concentration-dependently reduced KCl-induced [3H]GABA release, with IC50 values of 11 nM for LY354740, 80 nM for l (+)-2-amino-4-phosphonobutyric acid ( l -AP4), 180 nM for DCG-IV, and 330 nM for l -SOP. The group II antagonists, LY341495 and EGLU, reversed the effect of LY354740, and the group III antagonist MTPG reversed the effect of l -AP4. In the presence of ω-conotoxin GVIA, LY354740 inhibited the remaining [3H]GABA release, whereas l -AP4 was inactive. In contrast, in the presence of nifedipine, l -AP4 inhibited the remaining [3H]GABA release, but LY354740 was no longer active. The PKA inhibitor, H89, blocked the effects of both l -AP4 and LY354740, whereas the PKC inhibitor Ro 31-8220 blocked only the effect of LY354740. Both Ro 31-8220 and H89 reduced the [3H]GABA release to 60% of control. In whole-cell, voltage-clamp experiments, LY354740 and l -AP4 inhibited voltage-gated calcium channel currents with IC50 values of 28 nM and 22 μM, respectively. The results suggest that, in these cells, KCl-induced [3H]GABA release is modulated by two different mechanisms, one involving group II receptors and a direct control of the Ca2+ channel activity, and the other mediated by group III receptors and possibly involving a regulation located downstream of the Ca2+ channel activation. |
| Databáze: | OpenAIRE |
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