Open AccessRegeneration of beta-adrenergic receptors in senescent rats: a study using an irreversible binding antagonist.
Author(s) -
Josef Pitha,
Barbara A. Hughes,
John W. Kusiak,
Elizabeth M. Dax,
Stephen P. Baker
Publication year - 1982
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.79.14.4424
Subject(s) - alprenolol , receptor , adrenergic receptor , endocrinology , antagonist , blockade , medicine , dihydroalprenolol , pharmacology , iodocyanopindolol , chemistry , adrenergic , beta (programming language) , adrenergic antagonist , alpha 1d adrenergic receptor , biology , beta 3 adrenergic receptor , agonist , intrinsic activity , partial agonist , computer science , programming language
The drug used in this study, bromoacetylalprenololmenthane, has the ability to bind and block irreversibly beta-adrenergic receptors. The drug was bound to membranes prepared from hearts, lungs, and brains of both senescent and young rats with a similar affinity. When this drug was injected into rats in nontoxic doses (up to 70 mg/kg), up to 90% of beta-adrenergic receptors were irreversibly blocked 4 hr after injection, whereas the injection of similar amounts of (+/-)-alprenolol was without effect on receptor number. In senescent animals this blockade lasted considerably longer than in young animals; receptor numbers in hearts and lungs of senescent rats returned to control levels only 1 month after injection. The number of beta-adrenergic receptors in brains of senescent rats was unaffected by this drug. Thus, based upon the long-lasting blockade of beta-adrenergic receptors in therapeutically important organs, it appears that irreversible binding blockers may have potential in the treatments of senescent organisms.