Iodoazidobenzylpindolol, a photoaffinity probe for the beta-adrenergic receptor.

A high-affinity pindolol derivative, (+/-)-1-(indol-4-yloxy)-3-[1-(p-azido-m-iodophenyl)-2-isobutylamine]-2-propanol (IABP), has been prepared; it contains an iodide and an azide functional group and acts as a photoaffinity label for the beta-adrenergic receptor. When [125I]IABP (specific activity 1300 Ci/mmol) was photolyzed with crude duck erythrocyte membrane preparations, which contain beta-adrenergic receptor binding sites highly specific labeling of two polypeptides was observed upon electrophoresis on sodium dodecyl sulfate/polyacrylamide gels. These two polypeptides, A (Mr approximately 45,000) and B (Mr approximately 48,500), and B (Mr approximately 48,500), were photolabeled in a ratio of approximately 4:1 A/B. Binding of [125I]IABP and covalent derivatization of the beta receptor was at least 70% specific. The data indicate that [125I]IABP is a very effective compound for identification of polypeptides containing the beta-receptor binding site even in crude membrane preparations. The beta receptor of the duck erythrocyte plasma membrane may be composed of more than one subunit.