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σ‐Receptor Regulation of [ 3 H]Arachidonic Acid Release from Rat Neonatal Cerebellar Granule Cells in Culture
Author(s) -
Starr Jonathan B.,
Werling Linda L.
Publication year - 1994
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1994.63041311.x
Subject(s) - cerebellum , receptor , granule cell , arachidonic acid , agonist , biochemistry , chemistry , quisqualic acid , nmda receptor , biology , medicine , endocrinology , glutamate receptor , kainic acid , central nervous system , dentate gyrus , enzyme
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 [ 3 H]haloperidol binding. The excitatory amino acid N ‐methyl‐ d ‐aspartate and the direct phospholipase A 2 activator melittin stimulated the release of [ 3 H]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 σ 1 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 µ M 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.