Irreversible blockade of beta adrenoreceptors and their recovery in the rat heart and lung in vivo.

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.