External detection of beta-adrenoreceptors with 125I-hydroxybenzylpindolol in isolated perfused hearts.
To assess the feasibility of characterizing beta-adrenoreceptors externally with ligands labeled with gamma-emitting radionuclides, we infused 125I-hydroxybenzylpindolol (125I-HYP) a potent, high affinity, beta-adrenoreceptor ligand into isolated perfused hearts and monitored uptake and release of the label externally with a gamma probe. Perfusion with specific beta-adrenergic displacing significantly increased the turnover rate constant of 125I-HYP in comparison to that obtained with non-specific displacing agents. After modifying beta-adrenoreceptor density by pretreatment of animals with thyroid hormone, an increase in 125I-HYP uptake was observed. Thus, beta-adrenoreceptor occupancy and increases in beta-adrenoreceptor density can be detected externally with an approach which may offer promise for their characterization in vivo with radiolabeled adrenergic ligands.
D000818:Animals; D002415:Cats; D006321:Heart / Q000187:drug effects; D066298:In Vitro Techniques; D007457:Iodine Radioisotopes; D007700:Kinetics; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D010477:Perfusion; D010869:Pindolol / Q000031:analogs & derivatives* / Q000378:metabolism; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism*; D014284:Triiodothyronine / Q000494:pharmacology
D007457:Iodine Radioisotopes; D011943:Receptors, Adrenergic, beta; D014284:Triiodothyronine; C011878:iodohydroxybenzylpindolol; D010869:Pindolol