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Evidence for Metabotropic Excitatory Amino Acid Receptor Heterogeneity: Developmental and Brain Regional Studies
Author(s) -
Vecil Giacomo G.,
Li Peter P.,
Warsh Jerry J.
Publication year - 1992
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1992.tb08898.x
Subject(s) - neuroscience , excitatory postsynaptic potential , excitatory amino acid transporter , metabotropic glutamate receptor , biology , glutamate receptor , receptor , biochemistry , inhibitory postsynaptic potential
To examine whether multiple subtypes of the excitatory amino acid (EAA) receptor coupled to phosphoino‐sitide (PPI) hydrolysis exist, we have pharmacologically characterized the PPI response in neonatal and adult rat brain. Activation of PPI hydrolysis was determined by the accumulation of [ 3 H]inositol monophosphate in brain slices prelabeled with [ 3 H]inositol. In neonatal hippocampus, D,L‐2‐amino‐3‐phosphonopropionic acid (AP3; 1 m M ) inhibited the m‐1‐aminocyclopentane‐1,3‐dicarboxylic acid (IUPAC nomenclature; ACPD; 100 μ M)‐ and quisqualate (Quis; 100 μ M )‐stimulated PPI hydrolysis by 73 and 66%, respectively, but had no effect in neonatal cerebellum. In adult hippocampus, AP3 stimulated PPI hydrolysis with potency and efficacy comparable to those of Quis and ACPD and completely masked the Quis concentration‐response curve. In adult cerebellum, only Quis behaved as a full agonist on the PPI response. The Quis concentration‐response curve was shifted rightward with a fourfold decrease in potency in the presence of ACPD (5 m M ), whereas it was nearly additive with the PPI response induced by AP3 (5 m M ). Thus, our data reveal significant developmental and brain regional differences in metabotropic EAA receptor responses and support the notion that this receptor is heterogeneous, in both a regionally specific and a develop‐mentally dependent manner.