title: Beta receptor occupancy. Assessment in the intact animal.
abstract: Organ uptake of 125I-hydroxybenzylpindolol, a potent beta adrenergic antagonist, was determined after intravenous administration. Pretreatment with the beta agonist, epinephrine, inhibited an almost identical fraction of 125I-hydroxybenzylpindolol binding as did the antagonist, propranolol. Specific beta receptor binding accounted for 50% of total uptake in the lung and demonstrated the following characteristics. The dose-response curve for propranolol inhibition of 125I-hydroxybenzylpindolol binding duplicated that reported for its physiologic action. Simultaneous serum propranolol levels as determined by a sensitive radioimmunoassay allowed an apparent dissociation rate constant approximately 7 nM to be obtained that correlated closely with the results reported from membrane binding studies. Alpha blockade had no effect and inhibition of 125I-hydroxybenzylpindolol binding by propranolol demonstrated stereospecificity. After chemical sympathectomy with reserpine or 6-OH dopamine, there was a 100% increase in receptor specific binding. Finally, a scintillation camera was employed to visually and quantitatively detect 125I-hydroxybenzylpindolol displacement from the lung during intravenous propranolol administration in the living animal. Reversal of binding was rapid and an in vivo inhibition curve was generated. Such a method provides the potential for longitudinally assessing beta receptor occupancy and apparent affinity directly in man.
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000378:metabolism*; D000818:Animals; D004837:Epinephrine / Q000494:pharmacology; D006892:Hydroxydopamines / Q000494:pharmacology; D051379:Mice; D010646:Phentolamine / Q000494:pharmacology; D010869:Pindolol / Q000031:analogs & derivatives* / Q000378:metabolism; D011433:Propranolol / Q000494:pharmacology; D011941:Receptors, Adrenergic / Q000378:metabolism*; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D012110:Reserpine / Q000494:pharmacology; D013237:Stereoisomerism; D013564:Sympathetic Nervous System / Q000187:drug effects
chemical_list: D000319:Adrenergic beta-Antagonists; D006892:Hydroxydopamines; D011941:Receptors, Adrenergic; D011943:Receptors, Adrenergic, beta; C011878:iodohydroxybenzylpindolol; D012110:Reserpine; D011433:Propranolol; D010869:Pindolol; D004837:Epinephrine; D010646:Phentolamine