CHANGES OF PHARMACOLOGICAL PROPERTIES OF (1S,3R)-ACPD-SENSITIVE GLUTAMATE BINDING-SITES IN DEVELOPING MOUSE CEREBELLUM

Autoradiography of [H-3]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 [H-3]glutamate binding sit es and the sensitivity of these sites to drugs preferentially acting o n one or few types of the metabotropic receptor family. The inhibitory effect of (1S,3R)-ACPD on [H-3]glutamate binding and its estimated in hibition constant showed the presence of a different global metabotrop ic receptor population according to the region considered. During onto geny, 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 sens itivities to (RS)-alpha-methyl-4-carboxyphenylglycine (MCPG), (S)-4-ca rboxyphenylglycine (4-CPG), (2S,3S,4S)-alpha-(carboxycyclopropyl)glyci ne (L-CCG-I) and L-2-amino-4-phosphonobutyric acid (L-AP4) were demons trated according to the region and the age. In the DCN, the high (1S,3 R)-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-CP G- and the L-AP4-sensitive [H-3]glutamate binding sites appeared durin g ontogeny and the L-CCG-I-sensitive [H-3]glutamate binding sites were already present al PND 10. In the IGL, L-CCG-I-sensitive binding sire s disappeared in contrast to the L-AP4-sensitive binding sites which a ppeared during development even if the total (1S,3R)-ACPD binding site density was relatively weak in the adults. These results all reflecte d the multiplicity of the receptor subtypes included in the cerebellar metabotropic component.