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Kappa Receptor Activation Attenuates L-trans-pyrrolidine-2,4-dicarboxylic Acid-Evoked Glutamate Levels in the Striatum

Kappa Receptor Activation Attenuates L-trans-pyrrolidine-2,4-dicarboxylic Acid-Evoked Glutamate Levels in the Striatum

S M Rawls, J F McGinty

J Neurochem. 1998 Feb;70(2):626-34.

PMID: 9453556

Abstract:

The effects of local kappa receptor activation and blockade on extracellular striatal glutamate levels evoked by reverse microdialysis of L-trans-pyrrolidine-2,4-dicarboxylic acid (L-trans-PDC) were investigated. L-trans-PDC elevates extracellular glutamate levels in vivo by acting as a competitive substrate for plasma membrane excitatory amino acid transporters. The selective kappa-opioid receptor agonist U-69593 (1-100 nM) significantly attenuated L-trans-PDC-stimulated glutamate levels in a concentration-dependent manner. The selective kappa receptor antagonist nor-binaltorphimine (1-100 nM) reversed the U-69593-induced decrease in L-trans-PDC-evoked glutamate levels also in a concentration-dependent manner, indicating that the U-69593-induced reduction was mediated by kappa receptor activation. In addition, nor-binaltorphimine significantly elevated basal extracellular glutamate levels, implying that kappa receptors tonically regulate glutamate efflux in the striatum. Previous data from this laboratory have shown that L-trans-PDC-evoked extracellular glutamate levels are partially calcium-sensitive. The present study demonstrated that the inhibition of L-trans-PDC-evoked glutamate levels by reduced calcium perfusion was not altered by U-69593. Therefore, kappa receptors regulate the calcium-dependent component of L-trans-PDC-evoked extracellular glutamate levels in the striatum.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP64769660	L-trans-Pyrrolidine-2,4-dicarboxylic acid		64769-66-0	Price

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