Symptomatic and neuroprotective effects following activation of nigral group III metabotropic glutamate receptors in rodent models of Parkinson's disease.

British Journal of Pharmacology
P J AustinSusan Duty

Abstract

Increased glutamatergic innervation of the substantia nigra pars reticulata (SNpr) and pars compacta (SNpc) may contribute to the motor deficits and neurodegeneration, respectively, in Parkinson's disease (PD). This study aimed to establish whether activation of pre-synaptic group III metabotropic glutamate (mGlu) receptors reduced glutamate release in the SN, and provided symptomatic or neuroprotective relief in animal models of PD. Broad-spectrum group III mGlu receptor agonists, O-phospho-l-serine (l-SOP) and l-2-amino-4-phosphonobutyrate (l-AP4), were assessed for their ability to inhibit KCl-evoked [(3)H]-d-aspartate release in rat nigral prisms or inhibit KCl-evoked endogenous glutamate release in the SNpr in vivo using microdialysis. Reversal of akinesia in reserpine-treated rats was assessed following intranigral injection of l-SOP and l-AP4. Finally, the neuroprotective effect of 7 days' supra-nigral treatment with l-AP4 was examined in 6-hydroxydopamine (6-OHDA)-lesioned rats. l-SOP and l-AP4 inhibited [(3)H]-d-aspartate release by 33 and 44% respectively. These effects were blocked by the selective group III mGlu antagonist (RS)-alpha-cyclopropyl-4-phosphonophenylglycine (CPPG). l-SOP also reduced glutamate release i...Continue Reading

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Citations

Feb 18, 2010·Future Medicinal Chemistry·Corey R HopkinsColleen M Niswender
Oct 26, 2013·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Weidong LeJoseph Jankovic
Aug 26, 2014·Neurochemical Research·Marion S Mercier, David Lodge
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Nov 14, 2019·Frontiers in Pharmacology·Ilaria Dal PràAnna Chiarini
May 14, 2011·Current Opinion in Pediatrics

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