Metabotropic glutamate receptor heterogeneity in rat brain.

摘要: Metabotropic glutamate receptors (mGluRs) are G protein-linked that operate through the formation of different second messengers. Utilizing quantitative autoradiographic techniques, we have characterized [3H]glutamate binding to mGluRs in discrete regions adult rat brain. [3H]Glutamate binding, presence high concentrations alpha-amino-3-hydroxymethyl-4-isoxazolepropionic acid (10 microM), N-methyl-D-aspartate (100 and 2.5 mM calcium chloride (CaCl2), was saturable. Scatchard plots were linear all examined revealed similar affinity constants about 500 nM. The largest number sites found outer cerebral cortical layers pmol/mg protein). displaced by quisqualate, trans-1-amino-1,3-cyclopentane dicarboxylic (t-ACPD) (racemic mixture), (1S,3R)-ACPD but not (1R,3S)-ACPD. guanine nucleotide analogue guanosine-5'-O-(3-thio) triphosphate microM) reduced affecting total sites, as predicted for protein-coupled receptor sites. Quisqualate displacement curves always biphasic resolved two with Ki values low nanomolar (15 nM) micromolar (63 ranges. both absence microM suggesting quisqualate linked mGluRs. competition broad (Hill coefficient = 0.73) monophasic under conditions, range (14-116 acts on apparent affinities. regional distributions different. highest levels site cerebellar molecular layer. cortex. pharmacological profile distribution suggest quisqualate-sensitive components might correspond mGluR1/mGluR5 mGluR2/mGluR3 subgroups cloned mGluRs, respectively.