Changes of pharmacological properties of (1S,3R)-ACPD-sensitive glutamate binding sites in developing mouse cerebellum

Abstract

Autoradiography of [ 3H]glutamate binding to mouse cerebellar sections was used to study the distribution of (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid-((1S,3R)-ACPD) sensitive [ 3H]glutamate binding sites and the sensitivity of these sites to drugs preferentially acting on one or few types of the metabotropic receptor family. The inhibitory effect of (1S,3R)-ACPD on [ 3H]glutamate binding and its estimated inhibition constant showed the presence of a different global metabotropic receptor population according to the region considered. During ontogeny, the (1S,3R)-ACPD binding site density increased in the molecular layer (ML), in contrast it decreased in the internal granular layer (IGL) and the deep cerebellar nuclei (DCN). In addition, different sensitivities to (RS)-α-methyl-4-carboxyphenylglycine (MCPG), (S)-4-carboxyphenylglycine (4-CPG), (2S,3S,4S)-α-(carboxycyclopropyl)glycine (L-CCG-I) and l-2-amino-4-phosphonobutyric acid ( l-AP4) were demonstrated according to the region and the age. In the DCN, the high (1S,3R)-ACPD binding site density at PND 10 seems to be also sensitive to L-CCG-I but not to MCPG, 4-CPG or l-AP4. In the ML, the MCPG-, the 4-CPG- and the l-AP4-sensitive [ 3H]glutamate binding sites appeared during ontogeny and the L-CCG-I-sensitive [ 3H]glutamate binding sites were already present at PND 10. In the IGL, L-CCG-I-sensitive binding sites disappeared in contrast to the l-AP4-sensitive binding sites which appeared during development even if the total (1S,3R)-ACPD binding site density was relatively weak in the adults. These results all reflected the multiplicity of the receptor subtypes included in the cerebellar metabotropic component.