| 14623765 |
White AM, Kylanpaa RA, Christie LA, McIntosh SJ, Irving AJ, Platt B: Presynaptic group I metabotropic glutamate receptors modulate synaptic transmission in the rat superior colliculus via 4-AP sensitive K (+) channels. Br J Pharmacol. 2003 Dec;140(8):1421-33. Epub 2003 Nov 17.
1. Group I metabotropic glutamate receptors (mGluRs) are thought to be important modulators of neuronal function in the superior colliculus (SC). Here, we investigated the pharmacology and signalling mechanisms underlying group I mGluR-mediated inhibition of neuronal excitability and synaptic transmission in the rat SC slice. 2. The group I agonist (RS)-3,5-dihydroxyphenylglycine (DHPG) potently depressed synaptically evoked excitatory postsynaptic potentials (EPSPs), currents (EPSCs), and action potentials in a dose-dependent manner (IC50: 6.3 microm). This was strongly reduced by the broad-spectrum antagonist (+)-alpha-methyl-4-carboxyphenylglycine (MCPG, 1 mm, approximately 95% reduction), by the mGluR1 antagonist LY367385 (100 microm, approximately 80% reduction) but not by the mGluR5 antagonist 6-methyl-2-(phenylethynyl)-pyridine (MPEP, 1-100 microm). 3. The putative mGluR5-specific agonist (RS)-2-chloro-5-hydroxyphenylglycine (CHPG, 500 microm) also inhibited EPSPs. Interestingly, CHPG's actions were not blocked by MPEP, but LY367385 (100 microm) reduced the effect of CHPG by 50%. 4. Inhibition induced by DHPG was independent of phospholipase C (PLC)/protein kinase C pathways, and did not require intact intracellular Ca2+ stores. It was not abolished but enhanced by the GABAA antagonist bicuculline (5 microm), suggesting that DHPG's action was not due to facilitated inhibition or changes in neuronal network activity. 5. The K+ channel antagonist 4-aminopyridine (4-AP, 50-100 microm) converted the inhibitory effect of DHPG into facilitation. Paired-pulse depression was strongly reduced by DHPG, an effect that was also prevented by 4-AP. 6. Our data indicate that group I agonists regulate transmitter release, presumably via an autoreceptor in the SC. This receptor may be involved in adaptation to repetitive stimulation via a non-PLC mediated pathway. |
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