Premium
CONCENTRATION OF (±)‐PROPRANOLOL IN ISOLATED, PERFUSED LUNGS OF RAT
Author(s) -
DOLLERY C.T.,
JUNOD A.F.
Publication year - 1976
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1976.tb07657.x
Subject(s) - propranolol , imipramine , ouabain , lidocaine , perfusion , chlorpromazine , chemistry , metabolism , endocrinology , substrate (aquarium) , quinidine , medicine , pharmacology , biophysics , biology , biochemistry , anesthesia , sodium , pathology , ecology , alternative medicine , organic chemistry
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 μ m to 1 m m ; 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 m m 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.