Differential modulation of NMDA-stimulated [3H]dopamine release from rat striatum by neuropeptide Y and σ receptor ligands

Document Type

Journal Article

Publication Date

6-20-1997

Journal

Brain Research

Volume

760

Issue

1-2

DOI

10.1016/S0006-8993(97)00283-7

Keywords

σ Receptor; Dopamine release; Neuropeptide Y; PYX-1; Rat striatum

Abstract

Although the identity of the endogenous ligands for sigma (σ) receptors is unknown, neuropeptide Y (NPY) has been named as a possible candidate for a natural transmitter at these receptors. Using a superfusion system, we compared the effect of NPY on NMDA-stimulated [3H]dopamine release in rat striatum to that of the σ agonists (+)-pentazocine and BD737. In contrast to (+)-pentazocine- or BD737-mediated inhibition of release, NPY enhanced release. However, the same σ antagonists (BD1008, DuP734, haloperidol and DTG) that reverse (+)-pentazocine- or BD737-mediated inhibition, as well as a Y receptor antagonist, PYX-1, all reversed the enhancement. PYX-1 also reversed the (+)-pentazocine- and BD737-mediated inhibition of release. Peptide YY (PYY) and [Leu31,Pro34]NPY did not mimic the effect of NPY. NPY13-36 enhanced release to the same extent as NPY but the effect was not reversed by σ antagonists. Our findings are consistent with the potential role of NPY as an endogenous ligand for a subtype of σ receptor with characteristics different from Y1, Y2 and Y3 receptors but sensitive to PYX-1.

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