BETA-ADRENERGIC-RECEPTOR LABELING IN INTACT ANIMALS WITH HYDROXYBENZYLPINDOLOL-I-125

Abstract

After the i.v. administration to mice of 125I-hydroxybenzylpindolol (125I-HYP), a potent .beta. adrenergic antagonist, particulate bound radioactivity in brain, heart and lung is selectively associated with .beta. adrenergic receptor binding sites. The amount of total and bound radioactivity in these tissues is time dependent, reaching peak values at about 5 min after injection, and increases approximately linearly with increasing 125I-HYP doses. The lung has the highest levels of radioactivity and the highest proportion of bound to total radioactivity. The amount of specifically bound 125I-HYP is markedly reduced by simultaneously injecting a .beta. adrenergic agonist or antagonist, although the total amount of radioactivity in the tissues is not affected. The .beta. antagonist (-)-propranolol reduces specific 125I-HYP binding 50% at doses of 0.01, 0.03 and 0.004 mg/kg in brain, heart and lung, respectively. Specific 125I-HYP binding is stereospecific in these tissues as (+)-propranolol is only 1-2% as effective as (-)-propranolol in reducing binding. The .beta. agonist (-)-isoproterenol has ID50 [median inhibitory dose] values in the range of 2-20 mg/kg, whereas the .alpha. adrenergic antagonist, phentolamine, does not reduce 125I-HYP binding. Although some radioactivity is associated with particulate fractions from the liver, little, if any, specific binding of 125I-HYP to a .beta. adrenergic receptor is demonstrable. The characteristics of 125I-HYP binding in mouse heart, lung and brain are those expected for the recognition site of the .beta. adrenergic receptor and thus provide a method for labeling the .beta. adrenergic receptor in vivo.