Characteristics of (+/-)-[14C]-oxprenolol and (+/-)-[14C]-propranolol incorporation by rat lung slices

1 The uptake of (+/-)-[14C]-oxprenolol and (+/-)-[14C]propranolol has been studied in rat lung slices. The loss of these two radiolabelled beta-adrenoceptor antagonists from pre-loaded lung slices has also been studied. 2 Over the concentration range studied (3.3 x 10(-7)M to 1.7 x 10(-3)M) a biphasic uptake of both compounds was observed. At concentration below 1.5 x 10(-4)M approximately, there was some evidence of saturability, but at higher concentrations uptake appeared to be a linear function of drug concentration. 3 At concentrations of 6.6 x 10(-7)M and 1.7 x 10(-6)M respectively, the uptake of oxprenolol and propranolol was significantly reduced by low temperature, anaerobic conditions, incubation in NA+-free medium, and by the metabolic inhibitors potassium cyanide and 2,4-dinitrophenol. Ouabain had little or no effect. 4 At the same concentration, oxprenolol uptake was also inhibited in a concentration-dependent manner by propranolol, amphetamine, chlorpromazine and imipramine. Noradrenaline was without effect. 5 The loss of oxprenolol and propranolol from lung slices preloaded with the two compounds was fairly slow, with 60 to 70% of the drug originally taken up still remaining in the tissue after 30 min in fresh medium. 6 Possible mechanisms underlying the pulmonary accumulation of oxprenolol and propranolol are discussed.