CHARACTERISTICS OF (±)‐[14C]‐OXPRENOLOL AND (±)‐[14C]‐PROPRANOLOL INCORPORATION BY RAT LUNG SLICES

• DOI: 10.1111/j.1476-5381.1981.tb16780.x
• Publication Date: 2012-07-20T00:51:08Z
• Authors: BRIAN A. HEMSWORTH; JAMES A. STREET
• Keywords: Male; 0301 basic medicine; Dose-Response Relationship, Drug; Temperature; Oxprenolol; Rats, Inbred Strains; In Vitro Techniques; Propranolol; Rats; 03 medical and health sciences; Animals; Carbon Radioisotopes; Lung

The uptake of (±)‐[14C]‐oxprenolol and (±)‐[14C]‐propranolol has been studied in rat lung slices. The loss of these two radiolabelled β‐adrenoceptor antagonists from pre‐loaded lung slices has also been studied. Over the concentration range studied (3.3 × 10−7m to 1.7 × 10−3m) a biphasic uptake of both compounds was observed. At concentrations below 1.5 × 10−4m approximately, there was some evidence of saturability, but at higher concentrations uptake appeared to be a linear function of drug concentration. At concentrations of 6.6 × 10−7m and 1.7 × 10−6m 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. At the same concentration, oxprenolol uptake was also inhibited in a concentration‐dependent manner by propranolol, amphetamine, chlorpromazine and imipramine. Noradrenaline was without effect. 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. Possible mechanisms underlying the pulmonary accumulation of oxprenolol and propranolol are discussed.