High affinity non-beta-adrenoceptor binding of beta-adrenergic ligands.

Two types of saturable binding, besides the well-known non-specific binding, were found when hydrophobic ligands were used for investigating the vesiculization of beta-adrenoceptors on cultured HeLa and Chang liver cells. The first (compartment I) representing beta-adrenoceptors with high affinity ([3H]DHA 0.8 nM, 125I-CYP 27 pM) and low capacity (10-20 fmol/mg protein), the second (compartment II) had a rather high affinity ([3H]DHA 400 nM, 125I-CYP 30 nM) and a very high capacity (20 000-25 000 fmol/mg protein). The affinity of adrenergic agents for compartment II correlates very well (r = 0.9418) with the calculated hydrophobicity. It is concluded that these types of binding sites might interfere with the determination of adrenoceptor binding sites when hydrophobic ligands are used. When using hydrophobic ligands like these special care should be taken to avoid such interference.