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Pharmacological and Regional Characterization of [ 3 H]LY278584 Binding Sites in Human Brain
Author(s) -
AbiDargham Anissa,
Laruelle Marc,
Wong David T.,
Robertson David W.,
Weinberger Daniel R.,
Kleinman Joel E.
Publication year - 1993
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 - 10.1111/j.1471-4159.1993.tb03208.x
Subject(s) - nucleus accumbens , human brain , entorhinal cortex , caudate nucleus , hippocampus , population , receptor , putamen , binding site , chemistry , medicine , endocrinology , dopamine , neuroscience , biology , biochemistry , environmental health
Binding of [ 3 H]LY278584, which has been previously shown to label 5‐hydroxytryptamine 3 (5‐HT 3 ) receptors in rat cortex, was studied in human brain. Saturation experiments revealed a homogeneous population of saturable binding sites in amygdala ( K D = 3.08 ± 0.67 n M, B max = 11.86 ± 1.87 fmol/mg of protein) as well as in hippocampus, caudate, and putamen. Specific binding was also high in nucleus accumbens and entorhinal cortex. Specific binding was negligible in neocortical areas. Kinetic studies conducted in human hippocampus revealed a K on of 0.025 ± 0.009 n M −1 min −1 and a K off of 0.010 ± 0.002 min −1 . The kinetics of [ 3 H]LY278584 binding were similar in the caudate. Pharmacological characterization of [ 3 H]LY278584 specific binding in caudate and amygdala indicated the compound was binding to 5‐HT 3 receptors. We conclude that 5‐HT 3 receptors labeled by [ 3 H]LY278584 are present in both limbic and striatal areas in human brain, suggesting that 5‐HT 3 receptor antagonists may be able to influence the dopamine system in humans, similarly to their effects in rodent studies.