Characterization of 125I-lysergic acid diethylamide binding to serotonin receptors in rat frontal cortex.
125I-Lysergic acid diethylamide (125I-LSD) is the first 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 of 12.4 fmol/mg wet weight tissue, and a Hill slope of 1.02. The binding kinetics are highly temperature-dependent. At 37 degrees C the bimolecular association rate constant is 1.28 X 10(8) min-1 M-1 and the dissociation rate constant is 0.087 min-1 (t 1/2 = 8.0 min). At 0 degrees C less than 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 2,000 Ci/mmol, which makes them approximately 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.
D000818:Animals; D001667:Binding, Competitive; D002462:Cell Membrane / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism*; D007457:Iodine Radioisotopes; D007700:Kinetics; D008238:Lysergic Acid Diethylamide / Q000378:metabolism*; D051381:Rats; D011985:Receptors, Serotonin / Q000378:metabolism*
D007457:Iodine Radioisotopes; D011985:Receptors, Serotonin; D008238:Lysergic Acid Diethylamide