| Title: |
Native group‐III metabotropic glutamate receptors are coupled to the mitogen‐activated protein kinase/phosphatidylinositol‐3‐kinase pathways |
| Authors: |
Iacovelli, L.; Bruno, V.; Salvatore, L.; Melchiorri, D.; Gradini, R.; Caricasole, A.; Barletta, E.; De Blasi, A.; Nicoletti, F. |
| Source: |
Journal of Neurochemistry ; volume 82, issue 2, page 216-223 ; ISSN 0022-3042 1471-4159 |
| Publisher Information: |
Wiley |
| Publication Year: |
2002 |
| Collection: |
Wiley Online Library (Open Access Articles via Crossref) |
| Description: |
We used cultured cerebellar granule cells to examine whether native group‐III metabotropic glutamate (mGlu) receptors are coupled to the mitogen‐activated protein kinase (MAPK) and phosphatidylinositol‐3‐kinase (PI‐3‐K) pathways. Cultured granule cells responded to the group‐III mGlu receptor agonist, L ‐2‐amino‐4‐phosphonobutanoate ( l ‐AP4), with an increased phosphorylation and activity of MAPKs (ERK‐1 and ‐2) and an increased phosphorylation of the PI‐3‐K target, protein kinase B (PKB/AKT). These effects were attenuated by the group‐III antagonists, α‐methyl‐serine‐ O ‐phosphate (MSOP) and ( R,S )‐α‐cyclopropyl‐4‐phosphonophenylglycine (CPPG), or by pretreatment of the cultures with pertussis toxin. l ‐AP4 also induced the nuclear translocation of β‐catenin, a downstream effector of the PI‐3‐K pathway. To assess the functional relevance of these mechanisms we examined the ability of l ‐AP4 to protect granule cells against apoptosis by trophic deprivation, induced by lowering extracellular K + from 25 to 10 m m . Neuroprotection by l ‐AP4 was attenuated by MSOP and abrogated by the compounds PD98059 and UO126 , which inhibit the MAPK pathway, or by the compound LY294002, which inhibits the PI‐3‐K pathway. Taken together, these results show for the first time that native group‐III mGlu receptors are coupled to MAPK and PI‐3‐K, and that activation of both pathways is necessary for neuroprotection mediated by this particular class of receptors. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.1046/j.1471-4159.2002.00929.x |
| Availability: |
https://doi.org/10.1046/j.1471-4159.2002.00929.x; https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1046%2Fj.1471-4159.2002.00929.x; https://onlinelibrary.wiley.com/doi/pdf/10.1046/j.1471-4159.2002.00929.x |
| Rights: |
http://onlinelibrary.wiley.com/termsAndConditions#vor |
| Accession Number: |
edsbas.C23AFB30 |
| Database: |
BASE |