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.
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000375:Aging; D000526:Alprenolol / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000378:metabolism; D000081005:Cyclohexane Monoterpenes; D004082:Dihydroalprenolol / Q000378:metabolism; D007700:Kinetics; D008168:Lung / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011941:Receptors, Adrenergic / Q000378:metabolism*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism*
D000319:Adrenergic beta-Antagonists; D000081005:Cyclohexane Monoterpenes; D011941:Receptors, Adrenergic; D011943:Receptors, Adrenergic, beta; C028413:dihydroalprenolol receptor; D004082:Dihydroalprenolol; C028417:1-(2-allylphenoxy)-3-((8-bromoacetylamino-4-menthane-1-yl)amino)-1-propanol; C028416:1-(2-allylphenoxy)-3-((1-bromoacetylamino-4-menthane-8-yl)amino)-2-propanol; D000526:Alprenolol