Concentration of (+/-)-propranolol in isolated, perfused lungs of rat.
1 The metabolism and the accumulation of (+/-)-propranolol have been studied in isolated lungs of the rat, perfused with an artificial medium. 2 Little or no metabolism took place during the perfusion periods (up to 10 minutes). 3 Accumulation was observed with high tissue/medium ratios for substrate concentrations of 0.2 muM to 1 mM; there was evidence for saturability, but no real plateau could be seen. The presence of two binding sites with different affinities was established. 4 Cold greatly inhibited the accumulation process at low substrate concentrations, but had no effect at 1 mM propranolol. 5 Inhibition of accumulation was measured in the presence of imipramine, desmethylimipramine, nortryptiline, chlorpromazine and of Na+-free medium. Cocaine, 5-hydroxytryptamine and noradrenaline had no effect. Lidocaine enhanced the accumulation process. Release of previously bound propranolol was accelerated in the presence of propranolol and imipramine, unaffected by a Na+-free medium and decreased by cold and by lidocaine. 6 Experiments on lung tissue slices yielded qualitatively similar results to those obtained with perfused lungs. Ouabain and KCN had no or little effect on propranolol accumulation.
D000818:Animals; D000963:Antimetabolites / Q000494:pharmacology; D066298:In Vitro Techniques; D008094:Lithium / Q000494:pharmacology; D008168:Lung / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010477:Perfusion; D011433:Propranolol / Q000378:metabolism*; D011619:Psychotropic Drugs / Q000494:pharmacology; D051381:Rats; D012964:Sodium / Q000494:pharmacology; D013395:Sucrose / Q000494:pharmacology; D013696:Temperature
D000963:Antimetabolites; D011619:Psychotropic Drugs; D013395:Sucrose; D008094:Lithium; D012964:Sodium; D011433:Propranolol