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

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.