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Metabotropic glutamate receptor subtypes independently modulate neuronal intracellular calcium
Author(s) -
Maiese Kenneth,
Ahmad Ishtiaq,
TenBroeke Michelle,
Gallant Jennifer
Publication year - 1999
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/(sici)1097-4547(19990215)55:4<472::aid-jnr7>3.0.co;2-q
Subject(s) - metabotropic glutamate receptor , agonist , acpd , calcium in biology , glutamate receptor , chemistry , metabotropic glutamate receptor 2 , metabotropic receptor , intracellular , biology , pharmacology , receptor , biochemistry
Metabotropic glutamate receptors (mGluRs) modulate several G‐protein‐related signal transduction pathways including intracellular calcium (iCa 2+ ) that control both neuronal development and demise. As an initial investigation, we characterized the ability of specific mGluR subtypes to modulate iCa 2+ by using Fura‐2 microfluorometry in primary hippocampal neurons. Activation rather than inhibition of the metabotropic system with the group I and group II mGluR agonist 1S,3R‐1‐aminocyclopentane‐1,3‐dicarboxylic acid (ACPD), the specific group I agonist (S)‐3,5‐dihydroxyphenylglycine (DHPG), and the specific group II agonist (2S,1′S,2′S)‐2‐(carboxycyclopropyl)glycine (LCCG‐I) increased iCa 2+ with increasing concentrations. In contrast, the group III mGluR agonist, L(+)‐2‐amino‐4‐phosphonobutyric acid (L‐AP4) produced no significant increase in iCa 2+ . Through the pharmacological modulation of individual mGluR subtypes, we further examined the role of iCa 2+ release by the mGluR system. Release of iCa 2+ by both 1S,3R‐ACPD and LCCG‐I was prevented only through the administration of the antagonists (2S)‐α‐ethylglutamic acid (EGlu; mGluR2 and mGluR3) and (2S,1′S,2′S,3′R)‐2‐(2′‐carboxy‐3′‐phenylcyclopropyl)glycine (PCCG‐IV; mGluR2), suggesting that the mGluR2 subtype was responsible for the release of iCa 2+ . As a control, the group I antagonists, L(+)‐2‐amino‐3‐phosphonopropionic acid (L‐AP3) and (RS)‐1‐aminoindan‐1,5‐dicarboxylic acid (AIDA), prevented DHPG release of iCa 2+ but were ineffective against iCa 2+ release by 1S,3R‐ACPD. Although extracellular calcium influx did not significantly contribute to the release of iCa 2+ by the mGluR system, pharmacological inhibition of calcium‐induced calcium‐release‐sensitive calcium pools played a critical role in the release of iCa 2+ . Further characterization of the cellular calcium pools modulated by the mGluR subtypes may provide greater insight into the mechanisms that mediate neuronal function. J. Neurosci. Res. 55:472–485, 1999. © 1999 Wiley‐Liss, Inc.