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Enhancement of NMDA responses by group I metabotropic glutamate receptor activation in striatal neurones
Author(s) -
Pisani Antonio,
Calabresi Paolo,
Centonze Diego,
Bernardi Giorgio
Publication year - 1997
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0700999
Subject(s) - nmda receptor , metabotropic glutamate receptor , agonist , depolarization , metabotropic receptor , patch clamp , long term potentiation , acpd , glutamate receptor , voltage clamp , chemistry , pharmacology , membrane potential , biophysics , neuroscience , biology , electrophysiology , biochemistry , receptor
The interactions between N‐methyl‐ d ‐aspartate (NMDA) and metabotropic glutamate receptors (mGluRs) were investigated in striatal slices, by utilizing intracellular recordings, both in current‐ and voltage‐clamp mode. Bath‐application (50 μ m ) or focal application of NMDA induced a transient membrane depolarization, while in the voltage‐clamp mode, NMDA (50 μ m ) caused a transient inward current. Following bath‐application of the non‐selective mGluR agonist 1 S ,3 R ‐aminocyclopentane‐1,3‐dicarboxylic acid (1 S ,3 R ‐ACPD, 10 μ m ), NMDA responses were reversibly potentiated both in current (197±15% of control) and voltage‐clamp experiments (200±18% of control). Bath‐application of the group I mGluR agonist ( RS )‐3,5‐dihydroxyphenylglycine (3,5‐DHPG, 10–300 μ m ) resulted in a dose‐dependent potentiation of NMDA‐induced membrane depolarization (up to 400±33% of control). This potentiation was either prevented by preincubation with ( RS )‐α‐methyl‐4‐carboxyphenylglycine ( RS ‐α‐MCPG, 300 μ m ), or blocked when applied immediately after 3,5‐DHPG wash‐out. Neither (2 S ,1′ S ,2′ S )2‐(2′‐carboxycyclopropyl)glycine (L‐CCG I, up to 100 μ m ) nor (2 S ,1′ R ,2′ R ,3′ R )‐2‐(2,3‐dicarboxycyclopropyl)‐glycine (DCG‐IV, 1 μ m ), agonists for group II mGluRs caused any change in NMDA responses. Likewise, l ‐serine‐O‐phosphate ( l ‐SOP, 30 μ m ), agonist for group III mGluRs, did not affect the NMDA‐induced depolarization. The enhancement of the NMDA responses was mimicked by phorbol‐12,13‐diacetate (PDAc, 1 μ m ) which activates protein kinase C (PKC). The 3,5‐DHPG‐mediated potentiation of the NMDA‐induced depolarization was prevented by preincubation with staurosporine (100 n m ) or calphostin C (1 μ m ), antagonists of PKC. Electrophysiological responses to α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionate (AMPA) receptor activation were not affected by agonists for the three‐classes of mGluRs. The present data suggest that group I mGluRs exert a positive modulatory action on NMDA responses, probably through activation of PKC. This functional interaction in the striatum appears of crucial importance in the understanding of physiological and pathological events, such as synaptic plasticity and neuronal death, respectively.British Journal of Pharmacology (1997) 120 , 1007–1014; doi: 10.1038/sj.bjp.0700999