(2S,3S,4R)-2-CARBOXY-4-ISOPROPYL-3-PYRROLIDINEACETIC ACID

Description

Dihydrokainic acid (DHK) is an inhibitor of excitatory amino acid transporter 2 (EAAT2; K_i = 23 μM for glutamate uptake by COS cells expressing EAAT2). It is selective for EEAT2 over EAAT1 and EAAT3 (K_i = >3 mM for both). DHK microinfusion (5 nmol) into the rat infralimbic cortex reduces the time spent immobile in the forced swim test, indicating antidepressant-like behavior, an effect that is blocked by the AMPA receptor antagonist NBQX and the serotonin (5-HT) receptor subtype 5-HT_1A antagonist WAY-100635 . It also increases glutamate and serotonin levels and the expression of c-Fos in the dorsal raphe nucleus. In contrast, DHK microinjection (6.25 nmol) into the rat prefrontal cortex (PFC) increases the latency to drink sucrose in a sucrose intake test, indicating anhedonia-like behavior. It also impairs memory acquisition, consolidation, and retrieval in mice in the novel object recognition test.

Uses

Dihydrokainic acid has been used as a glutamate transporter (GLT-1) inhibitor in the glutamate uptake assay of astrocytes and glial cells. It may be used as a GLT-1 inhibitor in Lateral habenula (LHb).

Definition

ChEBI: Dihydrokainic acid is a dicarboxylic acid. It is functionally related to a kainic acid.

Biological Activity

EAAT2(GLT1)-selective non-transportable inhibitor of L-glutamate and L-aspartate uptake (K i = 23 μ M). 130-fold selective over EAAT1 and EAAT3 (K i > 3 mM). Also available as part of the Excitatory Amino Acid Transporter Inhibitor Tocriset™ .

Biochem/physiol Actions

Dihydrokainic favors neuronal cell death. It modulates anxiety and depression behaviors.

storage

Room temperature