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Characterization of 125 I‐Lysergic Acid Diethylamide Binding to Serotonin Receptors in Rat Frontal Cortex
Author(s) -
Kadan Michael J.,
Krohn Ann Marie,
Evans Mark J.,
Waltz Robin L.,
Hartig Paul R.
Publication year - 1984
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.1471-4159.1984.tb12777.x
Subject(s) - serotonergic , chemistry , dissociation constant , binding site , serotonin , receptor , ligand (biochemistry) , 5 ht receptor , receptor–ligand kinetics , lysergic acid diethylamide , stereochemistry , biophysics , medicine , endocrinology , biochemistry , biology
125 I‐Lysergic acid diethylamide ( 125 I‐LSD) is the first 125 I‐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 K D of 1.5 n M , a B max of 12.4 fmol/mg wet weight tissue, and a Hill slope of 1.02. The binding kinetics are highly temperature‐dependent. At 37°C the bimolecular association rate constant is 1.28 × 10 8 min −1 M −1 and the dissociation rate constant is 0.087 min −1 ( t 1/2 = 8.0 min). At 0°C < 4% dissociation occurs over 40 min and the association rate is similarly depressed. Inhibition of 125 I‐LSD binding by a variety of serotonergic, dopaminergic, and adrenergic ligands reveals a 5‐hydroxytryptamine 2 (5‐HT 2 ) serotonergic profile for this binding site. Regional distribution studies of 125 I‐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 125 I‐LSD for 5‐HT 2 sites, makes this ligand a sensitive new probe for 5‐HT 2 serotonin receptors.