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Cloning and characterization of alternative mRNA forms for the rat metabotropic glutamate receptors mGluR7 and mGluR8
Author(s) -
Corti Corrado,
Restituito Sophie,
Rimland Joseph M.,
Brabet Isabelle,
Corsi Mauro,
Pin Jean Philippe,
Ferraguti Francesco
Publication year - 1998
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1046/j.1460-9568.1998.00371.x
Subject(s) - metabotropic glutamate receptor , metabotropic glutamate receptor 6 , biology , metabotropic glutamate receptor 3 , metabotropic glutamate receptor 4 , metabotropic glutamate receptor 1 , metabotropic glutamate receptor 7 , metabotropic glutamate receptor 2 , metabotropic receptor , metabotropic glutamate receptor 5 , microbiology and biotechnology , gene isoform , alternative splicing , biochemistry , receptor , glutamate receptor , gene
Novel mRNA isoforms for two members of the group III metabotropic glutamate receptors (mGluRs), called mGluR7 b and mGluR8 b , were identified from rat brain cerebral cortex and hippocampus. In both cases, the alternative splicing is generated by a similar out‐of‐frame insertion in the carboxyl‐terminus that results in the replacement of the last 16 amino acids of mGluR7 and mGluR8 by 23 and 16 different amino acids, respectively. Distribution analysis for mGluR7 and mGluR8 isoforms revealed that the two splice variants are generally coexpressed in the same brain areas. The few exceptions were the olfactory bulb, in which only the mGluR7 a form could be detected by reverse transcription–polymerase chain reaction, and the lateral reticular and ambiguus nuclei, which showed only mGluR8 a labelling. Despite expression in the same regions, different mRNA abundance for the two variants of each receptor were observed. When transiently coexpressed in HEK 293 cells with the phospholipase C‐activating chimeric Gαqi9‐G‐protein, the a and b forms for both receptor subtypes showed a similar pharmacological profile. The rank order of potencies for both was: dl ‐amino‐4‐phosphonobutyrate > l ‐serine‐ O ‐phosphate > glutamate. However, the agonist potencies were significantly higher for mGluR8 a , b compared with mGluR7 a , b . In Xenopus oocytes, glutamate evoked currents only with mGluR8 when coexpressed with Kir 3.1 and 3.4. Glutamate‐induced currents were antagonized by the group II/III antagonist (RS)‐α‐cyclopropyl‐4‐phosphonophenylglycine. In conclusion, the two isoforms of each receptor have identical pharmacological profiles when expressed in heterologous systems, despite structural differences in the carboxyl‐terminal domains.