Regeneration of beta-adrenergic receptors in senescent rats: a study using an irreversible binding antagonist

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.