alexa Pharmacological and regional characterization of [3H]LY278584 binding sites in human brain.
Genetics & Molecular Biology

Genetics & Molecular Biology

Journal of Genetic Syndromes & Gene Therapy

Author(s): AbiDargham A, Laruelle M, Wong DT, Robertson DW, Weinberger DR,

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Abstract Binding of [3H]LY278584, which has been previously shown to label 5-hydroxytryptamine3 (5-HT3) receptors in rat cortex, was studied in human brain. Saturation experiments revealed a homogeneous population of saturable binding sites in amygdala (KD = 3.08 +/- 0.67 nM, Bmax = 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 Kon of 0.025 +/- 0.009 nM-1 min-1 and a Koff of 0.010 +/- 0.002 min-1. The kinetics of [3H]LY278584 binding were similar in the caudate. Pharmacological characterization of [3H]-LY278584 specific binding in caudate and amygdala indicated the compound was binding to 5-HT3 receptors. We conclude that 5-HT3 receptors labeled by [3H]LY278584 are present in both limbic and striatal areas in human brain, suggesting that 5-HT3 receptor antagonists may be able to influence the dopamine system in humans, similarly to their effects in rodent studies.
This article was published in J Neurochem and referenced in Journal of Genetic Syndromes & Gene Therapy

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