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Novel metabotropic glutamate receptor negatively coupled to adenylyl cyclase in cultured rat cerebellar astrocytes
Author(s) -
Kanumilli Srinivasan,
Toms Nick J.,
Roberts Peter J.
Publication year - 2003
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/glia.10339
Subject(s) - kainate receptor , metabotropic glutamate receptor 1 , metabotropic glutamate receptor 6 , metabotropic glutamate receptor 5 , biology , metabotropic glutamate receptor , glutamate receptor , adenylyl cyclase , ampa receptor , metabotropic glutamate receptor 7 , metabotropic receptor , biochemistry , receptor
Abstract Several excitatory amino acid ligands were found potently to inhibit forskolin‐stimulated cAMP accumulation in rat cultured cerebellar astrocytes: L ‐cysteine sulfinic acid ( L ‐CSA) = L ‐aspartate > L ‐glutamate ≥ the glutamate uptake inhibitor, L ‐PDC. This property did not reflect activation of conventional glutamate receptors, since the selective ionotropic glutamate receptor agonists NMDA, AMPA, and kainate, as well as several mGlu receptor agonists [(1S,3R)‐ACPD, (S)‐DHPG, DCG‐IV, L ‐AP4, L ‐quisqualate, and L ‐CCG‐I], were without activity. In addition, the mGlu receptor antagonists, L ‐AP3, (S)‐4CPG, Eglu, LY341495, (RS)‐CPPG, and (S)‐MCPG failed to reverse 30 μM glutamate‐mediated inhibitory responses. L ‐PDC‐mediated inhibition was abolished by the addition of the enzyme glutamate‐pyruvate transaminase. This finding suggests that the effect of L ‐PDC is indirect and that it is mediated through endogenously released L ‐glutamate. Interestingly, L ‐glutamate‐mediated inhibitory responses were resistant to pertussis toxin, suggesting that G i /G o type G proteins were not involved. However, inhibition of protein kinase C (PKC, either via the selective PKC inhibitor GF109203X or chronic PMA treatment) augmented glutamate‐mediated inhibitory responses. Although mGlu3 receptors (which are negatively coupled to adenylyl cyclase) are expressed in astrocyte populations, in our study Western blot analysis indicated that this receptor type was not expressed in cerebellar astrocytes. We therefore suggest that cerebellar astrocytes express a novel mGlu receptor, which is negatively coupled to adenylyl cyclase, and possesses an atypical pharmacological profile. © 2003 Wiley‐Liss, Inc.