Characterization of (2S,2′R,3′R)‐2‐(2′,3′‐[3H]‐Dicarboxycyclopropyl)glycine Binding in Rat Brain

: [(2S,2′R,3′R)‐2‐(2′,3′‐[3H]Dicarboxycyclopropyl)glycine ([3H]DCG IV) binding was characterized in vitro in rat brain cortex homogenates and rat brain sections. In cortex homogenates, the binding was saturable and the saturation isotherm indicated the presence of a single binding site with a KD value of 180 ± 33 nM and a Bmax of 780 ± 70 fmol/mg of protein. The nonspecific binding, measured using 100 µM LY354740, was DCG IV = (2S,1′S,2′S)‐2‐(2‐carboxycyclopropyl)glycine > (1S,3R)‐1‐aminocyclopentane‐1,3‐dicarboxylic acid > (2S,1′S,2′S)‐2‐methyl‐2‐(2‐carboxycyclopropyl)glycine > l‐glutamate = ibotenate > quisqualate > (RS)‐α‐methyl‐4‐phosphonophenylglycine = l(+)‐2‐amino‐3‐phosphonopropionic acid > (S)‐α‐methyl‐4‐carboxyphenylglycine > (2S)‐α‐ethylglutamic acid > l(+)‐2‐amino‐4‐phosphonobutyric acid. N‐Acetyl‐l‐aspartyl‐l‐glutamic acid inhibited the binding in a biphasic manner with an IC50 of 0.2 µM for the high‐affinity component. The binding was also affected by GTPγS, reducing agents, and CdCl2. In parasagittal sections of rat brain, a high density of specific binding was observed in the accessory olfactory bulb, cortical regions (layers 1, 3, and 4 > 2, 5, and 6), caudate putamen, molecular layers of the hippocampus and dentate gyrus, subiculum, presubiculum, retrosplenial cortex, anteroventral thalamic nuclei, and cerebellar granular layer, reflecting its preferential (perhaps not exclusive) affinity for pre‐ and postsynaptic metabotropic glutamate mGlu2 receptors. Thus, the pharmacology, tissue distribution, and sensitivity to GTPγS show that [3H]DCG IV binding is probably to group II metabotropic glutamate receptors in rat brain.