Characterization of 125I‐Lysergic Acid Diethylamide Binding to Serotonin Receptors in Rat Frontal Cortex

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Abstract
125LSD is 1st 125I-labeled ligand for serotonin receptor studies. Its binding to rat frontal cortex membranes is saturable, reversible and stereospecific. Specific binding is linearly dependent on tissue concentration and represents 70-80% of the total binding. Scatchard plots of the binding data are linear with a KD of 1.5 nM, a Bmax [maximum binding] of 12.4 fmol/mg wet weight tissue, and a Hill slope of 1.02. The binding kinetics are highly temperature-dependent. At 37.degree. C the bimolecular association rate constant is 0.087 min-1 (t11/2 = 8.0 min). At 0.degree. C < 4% dissociation occurs over 40 min and the association rate is similarly depressed. Inhibition of 125I-LSD binding by a variety of serotonergic, dopaminergic and adrenergic ligands reveals a 5-hydroxytryptamine2 (5-HT2) serotonergic profile for this binding site. Regional distribution studies of 125I-LSD binding in rat brain show that areas with the highest levels of binding include the cortex and striatum. Iodinated radioligands can be synthesized with specific activities exceeding 2000 Ci/mmol, which makes them .apprx. 75-fold more sensitive than tritiated radioligands. This high specific activity, coupled with the selectivity of 125I-LSD for 5-HT2 sites, makes this ligand a sensitive new probe for 5-HT2 serotonin receptors.