Evidence for Distinct 5‐Hydroxytryptamine 2 Binding Site Subtypes in Cortical Membrane Preparations

5‐Hydroxytryptamine (5‐HT) displays a sixfold higher affinity for 5‐HT 2 binding sites labeled by [ 3 H]ketanserin in rat (IC 50 = 200 ± 40 n M ) and human (IC 50 = 190 ± 50 n M ) cortex than for 5‐HT 2 sites in bovine cortex (IC 50 = 1,200 ± 130 n M ). 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 (±)‐( 3 H]4‐bromo‐2,5‐dimethoxyamphetamine ([ 3 H]DOB) binding in the rat indicates a population of binding sites with a K D of 0.38 ± 0.04 n M and a B max of 1.5 ± 0.05 pmol/g tissue. In contrast, specific [ 3 H]DOB binding cannot be detected in bovine cortical membranes. These data indicate that species variations exist in 5‐HT 2 binding site subtypes and that [ 3 H]ketanserin appears to label a homogeneous population of 5‐HT 2 binding site subtypes in bovine cortex.