title: Irreversible blockade of beta adrenoreceptors and their recovery in the rat heart and lung in vivo.
abstract: The interaction of a bromoacetylated derivative of alprenolol (Alm-CO-CH2Br) with cardiac and lung beta adrenoreceptors was partially characterized. After a short incubation period, the concentration of Alm-CO-CH2Br that inhibited specific [3H]dihydroalprenolol binding by 50% in cardiac and lung membranes was 0.5 and 0.11 microM, respectively. The blockade was time-dependent and Scatchard analysis showed no change in the KD value for specific (-)-[3H]dihydroalprenolol binding but a loss of beta adrenoreceptor content after membrane pretreatment with Alm-CO-CH2Br. The blockade was not reversed by extensive membrane washing, although concurrent treatment with alprenolol fully protected whereas phentolamine had no protective effect. Alm-CO-CH2Br produced a dose-dependent blockade of heart and lung beta adrenoreceptors in vivo and the compound had little or no effect on the growth rate of the rat. Four hours after a single i.p. injection of Alm-CO-CH2Br at 35 mg/kg, the heart and lung beta adrenoreceptor content was decreased by 88 and 90%, respectively. The time required for complete recovery from irreversible beta adrenoreceptor blockade was about 200 hr in the heart and 650 hr in the lung. These results suggest that Alm-CO-CH2Br may be a useful probe for the beta adrenoreceptor both in vitro and for recovery studies in vivo.
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000378:metabolism* / Q000494:pharmacology; D000526:Alprenolol / Q000031:analogs & derivatives* / Q000378:metabolism; D000818:Animals; D002458:Cell Fractionation; D008168:Lung / Q000378:metabolism*; D008297:Male; D008566:Membranes / 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*
chemical_list: D000319:Adrenergic beta-Antagonists; D011941:Receptors, Adrenergic; D011943:Receptors, Adrenergic, beta; D000526:Alprenolol