RGD Reference Report - The inhibition of glutamate release by metabotropic glutamate receptor 7 affects both [Ca2+]c and cAMP: evidence for a strong reduction of Ca2+ entry in single nerve terminals. - Rat Genome Database

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The inhibition of glutamate release by metabotropic glutamate receptor 7 affects both [Ca2+]c and cAMP: evidence for a strong reduction of Ca2+ entry in single nerve terminals.

Authors: Millan, C  Lujan, R  Shigemoto, R  Sanchez-Prieto, J 
Citation: Millan C, etal., J Biol Chem 2002 Apr 19;277(16):14092-101.
RGD ID: 728749
Pubmed: PMID:11825890   (View Abstract at PubMed)
DOI: DOI:10.1074/jbc.M109044200   (Journal Full-text)

Metabotropic glutamate receptors (mGluRs) from group III reduce glutamate release. Because these receptors reduce cAMP levels, we explored whether this signaling pathway contributes to release inhibition caused by mGluRs with low affinity for L-2-amino-4-phosphonobutyrate (L-AP4). In biochemical experiments with the population of cerebrocortical nerve terminals we find that L-AP4 (1 mm) inhibited the Ca(2+)-dependent-evoked release of glutamate by 25%. This inhibitory effect was largely prevented by the pertussis toxin but was insensitive to inhibitors of protein kinase C bisindolylmaleimide and protein kinase A H-89. Furthermore, this inhibition was associated with reduction in N-type Ca(2+) channel activity in the absence of any detectable change in cAMP levels. In the presence of forskolin, however, L-AP4 decreased the levels of cAMP. The activation of this additional signaling pathway was very efficient in counteracting the facilitation of glutamate release induced either by forskolin or the beta-adrenergic receptor agonist isoproterenol. Imaging experiments to measure Ca(2+) dynamics in single nerve terminals showed that L-AP4 strongly reduced the Ca(2+) response in 28% of the nerve terminals. Moreover, immunochemical experiments showed that 25-35% of the nerve terminals that were immunopositive to synaptophysin were also immunoreactive to the low affinity L-AP4-sensitive mGluR7. Then, mGluR7 mediates the inhibition of glutamate release caused by 1 mm L-AP4, primarily by a strong inhibition of Ca(2+) channels, although high cAMP uncovers the receptor ability to decrease cAMP.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

Cellular Component
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
axon terminus  IDA 728749 RGD 

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
adenylate cyclase inhibiting G protein-coupled glutamate receptor activity  IDA 728749 RGD 
glutamate binding  IDA 728749L-2-amino-4-phosphonobutyrate L-AP4 and glutamate analogueRGD 
group III metabotropic glutamate receptor activity  TAS 728749 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Grm7  (glutamate metabotropic receptor 7)


Additional Information