Evidence for Distinct 5‐Hydroxytryptamine2 Binding Site Subtypes in Cortical Membrane Preparations

Abstract
5-Hydroxytryptamine (5-HT) displays a sixfold higher affinity for 5-HT, binding sites labeled by [3H]ketanserin in rat (IC50 = 200 .+-. 40 nM) and human (IC50 = 190 .+-. 50 nM) cortex than for 5-HT2 sites in bovine cortex (IC50 = 1,200 .+-. 130 nM). The Hill slopes of the 5-HT competition curves are 0.67 .+-. 0.04 in rat, 0.69 .+-. 0.08 in human, and 0.96 .+-. 0.02 in bovine cortex. Scatchard analysis of(.+-.)-[3H]4-bromo-2,5-dimethoxyamphetamine ([3H]DOB) binding in the rat indicates a population of binding sites with a KD of 0.38 .+-. 0.04 nM and a Bmax of 1.5.+-.0.05 pmol/g tissue. In contrast, specific [3H]DOB binding cannot be detected in bovine cortical membranes. These data indicate that species variations exist in 5-HT2 binding site subtypes and that [3H]ketanserin appears to label a homogeneous population of 5-HT2 binding site subtypes in bovine cortex.