The drug used in this study, bromoacetylalprenololmenthane, has the ability to bind and block irreversibly a-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 P-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 (3-adrenergic receptors in brains of senescent rats was unaffected by this drug. Thus, based upon the long-lasting blockade of -adrenergic receptors in therapeutically important organs, it appears that irreversible binding blockers may have potential in the treatments ofsenescent organisms.3-Adrenergic antagonists continue to be one of the main medications used to treat hypertension (1)-a symptom afflicting about one-third of a population sample of the elderly in the United States (2). The effects and also fate of these antagonists show changes with age (3) that are difficult to explain on the basis ofwhat is known about the age-related features ofthe adrenergic system (1,(4)(5)(6). In this work we studied the regeneration ofreceptors for these antagonists in senescent rats. Such a study can provide information concerning possible development of longer acting antagonists (7) and may eventually help in the clarification ofage effects on the adrenergic system. Bromoacetylalprenololmenthane, whose structure is given in Fig. 1, was used in this study. It was shown previously that this drug binds, at first reversibly, to a binding site of the p-adrenergic receptor and this reversible complex is transformed rapidly through a chemical reaction into a covalent receptor-drug complex that does not further bind molecules of agonists or antagonists (8). Furthermore, this drug has the advantage of high affinity for 3adrenergic receptors (8), as compared to similar compounds (9). Utilization of this drug in senescent rats revealed that the receptor number in some therapeutically important organs-such as heart and lung-remains below control levels for as long as 1 month after treatment. Thus, in senescence the rate ofregeneration, and probably the rate ofde novo synthesis of receptors, is low. The results point to the possibility of using irreversible blockade to perform "molecular surgery"-i.e., to excise part of the receptors in a senescent organism in a reasonably selective way and in a practically permanent manner. MATERIALS AND METHODSThe senescent animals, unless otherwise stated, were 27-month-old Sprague-Dawley rats that have a 2-yr median lifespan and were obtained from Harlan Industries (Indianapolis, IN). The animals used in the regeneration experiment were divided into groups of (i) drug tre...

The method presented here is recommended for the semiquantitative determination of nineteen volatile priority pollutants in raw and treated surface water, groundwater, and industrial effluents.

Copolymerization of acrylamide with ally1 glycidyl ether yielded water soluble polymers containing an epoxy group; addition of a crosslinking agent, ~,N'-methylenebis(acryl~de), to the copolymerization mixtures resulted in the formation of similar though water insoluble polymers. Condensation of a potent beta-adrenergic antagonist Alm-H, which contains a reactive amino group, with a polymer containing an epoxy group yielded a pharmacologically active polymer. The polymer containing the epoxy group was also converted, by reaction with sodium thiosulfate and subsequent reduction, into a mercapto groups containing polymer which was also water soluble. The latter polymer was converted by condensation with a beta-adrenergic antagonist Alm-COCH,Br, which contains a reactive bromoacetamido group, into a pharmacologically active polymer. 0025-1 16X/82/04

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