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Functional and Binding Properties of σ Receptors in Rat Cerebellum
Author(s) -
GonzalezAlvear Grace M.,
ThompsonMontgomery DeDeene,
Deben Sophia E.,
Werling Linda L.
Publication year - 1995
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.1471-4159.1995.65062509.x
Subject(s) - cerebellum , locus coeruleus , phencyclidine , neuroscience , receptor , nmda receptor , glutamate receptor , long term depression , norepinephrine , biology , chemistry , central nervous system , ampa receptor , dopamine , biochemistry
Autoradiographic studies have shown that σ receptors are enriched in the locus coeruleus, the origin of noradrenergic projections to the cerebellum, as well as in the Purkinje, molecular, and granular layers and the interpositus cerebellar nucleus of the cerebellum itself. In contrast, the cerebellum is relatively poor in phencyclidine (PCP) binding sites, which have been historically confused with σ sites. The high ratio of σ to PCP receptors in cerebellum is advantageous for discriminating σ‐mediated physiological effects. σ agonists and antagonists have been shown to regulate N ‐methyl‐ d ‐aspartate (NMDA)‐stimulated norepinephrine release in hippocampus, which is innervated by locus coeruleus projections. We now report that σ drugs also regulate norepinephrine release from cerebellum. In contrast to findings in the hippocampus, where regulation is via σ 1 and σ 2 receptors, σ‐mediated regulation in cerebellum seems to be primarily via σ 1 receptors. In radioligand binding studies, we find that σ receptors primarily of the σ 1 type are present in the cerebellum. We further report that binding to σ receptors in cerebellum is not affected by the addition of NMDA or glycine or by the presence of NMDA antagonists, suggesting that σ receptors are not located within the NMDA‐operated cation channel in this brain region.