Developmental regulation of metabotropic glutamate receptor 5b protein in rodent brain

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The metabotropic glutamate receptor type 5 (mGlu5) is expressed in two splice variants, mGlu5a and mGlu5b, which differ in that mGlu5b has a 33-amino acid insert in the intracellular C-terminal domain. This receptor subtype is highly regulated, with higher levels found in developing animals, but the contributions of the individual splice variants to the receptor population at any time are unknown. An antibody that specifically reacts with the insert was developed and used to measure the regional and developmental distribution of mGlu5b in the mouse and rat brain. In contrast to total mGlu5 receptor protein, most brain regions exhibit a less than two-fold alteration between post-natal day 7 and adult levels of mGlu5b. In the adult cortex, there is a three-fold increase of mGlu5b protein relative to at post-natal day 7. Estimates of mGlu5a protein indicate that most of the developmental alteration in total mGlu5 is due to changes in expression of this variant. Comparison of mGlu5b protein and mRNA levels indicates that greatly different post-transcriptional regulation occurs across brain regions. These results indicate that mGlu5 expression is precisely and complexly controlled at the level of transcription and that different functions of mGlu5 during different developmental periods and in distinct regions are likely mediated by different splice variants.