σ‐Receptor Regulation of [3H]Arachidonic Acid Release from Rat Neonatal Cerebellar Granule Cells in Culture

Document Type

Journal Article

Publication Date

1-1-1994

Journal

Journal of Neurochemistry

Volume

63

Issue

4

DOI

10.1046/j.1471-4159.1994.63041311.x

Keywords

(+)‐Pentazocine; Arachidonic acid release; Cerebellar granule cells; NMDA receptor; Phospholipase A 2; σ Receptor

Abstract

Abstract: σ receptors have been identified in many brain areas and are especially abundant in those regions known to be involved in control of movement. σ receptors have been located autoradiographically in the granule cell layer of cerebellum in adult rat brain. In the current study, we identified σ receptors in rat neonatal granule cells in culture using radioligand binding. The tritium labeled form of the putative σ antagonist haloperidol bound with high affinity to membranes prepared from these cells, and ligands selective for σ receptors competed well against [3H]haloperidol binding. The excitatory amino acid N‐methyl‐d‐aspartate and the direct phospholipase A2 activator melittin stimulated the release of [3H]arachidonic acid from cerebellar granule cells. The N‐methyl‐d‐aspartate‐stimulated, but not the melittin‐stimulated, release was inhibited in a concentration‐dependent manner by the σ‐selective agonist (+)‐pentazocine. In addition, the novel σ1 agonist BD737 inhibited N‐methyl‐d‐aspartate‐stimulated release. Pentazocine inhibition was almost completely reversed by the σ antagonists NPC‐16377 and opipramol. A 1 µM concentration of the phencyclidine receptor‐selective ligand MK‐801 inhibited ∼65% of N‐methyl‐d‐aspartate‐stimulated release. These results suggest that σ receptors may play a role in modulating arachidonic acid release in cerebellar granule cells. Copyright © 1994, Wiley Blackwell. All rights reserved

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