Stimulatory effects of the putative metabotropic glutamate receptor antagonist L‐AP3 on phosphoinositide turnover in neonatal rat cerebral cortex

Mistry, Rajendra; Prabhu, Greeshma S; Godwin, Mbaka; Challiss, R. A. John

doi:10.1111/j.1476-5381.1996.tb16730.x

Cited by 8 publications

(3 citation statements)

References 41 publications

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“…In the developing and adult cortex, trans-ACPD increases PI turnover (Mortensen et al, 1995;Bevilacqua et al, 1995) and intracellular Ca 2ϩ concentration (Koh et al, 1991b) in cortical neurons. The increase in PI turnover is reduced by L-AP-3 (Mortensen et al, 1995;Mistry et al, 1996). It is also known that 1S,3R-ACPD up to 1 mM is not neurotoxic for cortical neurons (Koh et al, 1991a) and even protects cortical neurons from NMDA-induced neurotoxicity (Koh et al, 1991b).…”

Section: Second Messenger Pathways Involved In the Regulation Of The mentioning

confidence: 99%

Regulation of the Nigrostriatal Pathway by Metabotropic Glutamate Receptors during Development

Plenz

Kitai

1998

J. Neurosci.

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Dopamine neurons in the substantia nigra heavily innervate the striatum, making it the nucleus with the highest levels of dopamine in the adult brain. The present study analyzes the time course and the density of striatal innervation by nigral dopamine neurons and characterizes the role of the neurotransmitter glutamate during the development of the nigrostriatal pathway. For this purpose, organotypic cultures containing the cortex, the striatum, and the substantia nigra (triple cultures) were prepared from rat brains at postnatal day (PND) 0-2 and were cultured for up to 60 d in vitro (DIV). Dopamine fibers and neurons were labeled using tyrosine hydroxylase (TH) immunohistochemistry. Striatal TH-ir fiber density was quantitatively analyzed using confocal laser scanning microscopy (CLSM). In long-term triple cultures (44 +/- 3 DIV), the striatal dopamine fiber density was high and was weakly correlated with the number of nigral dopamine neurons. The high striatal dopamine fiber density mainly resulted from an enhanced ingrowth and ramification of dopamine fibers from nigral neurons during 8-17 DIV. The metabotropic glutamate receptor (mGluR) antagonist L(+)-2-amino-3-phosphonopropionic acid (L-AP-3) selectively inhibited this dopaminergic innervation of the striatum, whereas ionotropic GluR antagonists had no effect. The L-AP-3-mediated inhibition was prevented by the mGluR agonist 1S, 3R-aminocyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD). The inhibition of the striatal dopaminergic innervation by L-AP-3 was further confirmed by anterograde tracing of the nigrostriatal projection with Phaseolus vulgaris leucoagglutinin. These results indicate that glutamate, by acting on group I mGluRs, plays an important "trophic" role for the development of the nigrostriatal dopamine pathway.

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Section: Second Messenger Pathways Involved In the Regulation Of The mentioning

confidence: 99%

Regulation of the Nigrostriatal Pathway by Metabotropic Glutamate Receptors during Development

Plenz

Kitai

1998

J. Neurosci.

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“…We investigated the effects of various antagonists of mGluRs on LTD induced by LFS of layer IV in the presence of APV. APV plus 300 M L-AP3, an antagonist of group I mGluRs (Mistry et al 1996), suppressed LTD significantly (P Ͻ 0.05, Fig. 8).…”

Section: Subtypes Of Mglurs Required For the Induction Of Ltdmentioning

confidence: 99%

Differential Dependence of LTD on Glutamate Receptors in the Auditory Cortical Synapses of Cortical and Thalamic Inputs

Kudoh

Sakai

Shibuki

2002

Journal of Neurophysiology

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Kudoh, Masaharu, Masashi Sakai, and Katsuei Shibuki. Differential dependence of LTD on glutamate receptors in the auditory cortical synapses of cortical and thalamic inputs. J Neurophysiol 88: 3167-3174, 2002. 10.1152/jn.00928.2001. Pyramidal neurons in the auditory cortex (AC) receive glutamatergic inputs from the medial geniculate body (MGB inputs) and other pyramidal neurons (pyramidal inputs). We found that the induction of long-term depression (LTD) in supragranular layers was only partially suppressed by 50 M D-(Ϫ)-2-amino-5-phosphonovalerate (APV), an antagonist of Nmethyl-D-aspartate (NMDA) receptors (NMDARs), and 500 M (ϩ)-␣-methyl-4-carboxyphenylglycine (MCPG), an antagonist of metabotropic glutamate receptors (mGluRs). However, LTD was not observed in the mixture of APV and MCPG. We hypothesized that the mixed dependence of LTD on glutamate receptors could be attributed to the heterogeneity of MGB inputs and pyramidal inputs. To test this hypothesis, the angle of slicing and other recording conditions were adjusted so that postsynaptic potentials were recorded in normal slices, but not in the slices prepared from the rats with MGB lesion. In these experiments, LTD was suppressed by MCPG alone. The conditions were adjusted to minimize the contribution of MGB inputs in field potentials. In these experiments, the induction of LTD was suppressed by APV alone. Interestingly, the induction of LTD was partially suppressed by 20 M nifedipine, a blocker of L-type Ca 2ϩ channels, in the slices prepared from the rats with MGB lesions, but not in normal slices. These findings suggest that the induction of LTD requires activation of mGluRs in the synapses of MGB inputs and of NMDARs in the synapses of pyramidal inputs.

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“…2A). This increase in iCa 2ϩ with the concentration of L-AP3 of 1,000 µM may be secondary to the ability of L-AP3 to act as a partial agonist on mGluRs with increased concentrations (Mistry et al, 1996). Although more specific and potent as an antagonist, administration of AIDA in the concentrations of 50 µM, 250 µM, 750 µM, and 1,000 µM produced no significant change over baseline iCa 2ϩ release (Fig.…”

Section: Inhibition Of the Mglurs Does Not Significantly Alter Neuronmentioning

confidence: 88%

Metabotropic glutamate receptor subtypes independently modulate neuronal intracellular calcium

et al. 1999

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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)-alpha-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.

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Stimulatory effects of the putative metabotropic glutamate receptor antagonist L‐AP3 on phosphoinositide turnover in neonatal rat cerebral cortex

Cited by 8 publications

References 41 publications

Regulation of the Nigrostriatal Pathway by Metabotropic Glutamate Receptors during Development

Regulation of the Nigrostriatal Pathway by Metabotropic Glutamate Receptors during Development

Differential Dependence of LTD on Glutamate Receptors in the Auditory Cortical Synapses of Cortical and Thalamic Inputs

Metabotropic glutamate receptor subtypes independently modulate neuronal intracellular calcium

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