Binding of Propranolol and Chlorpromazine by Mitochondrial Membranes.

Huunan-Seppälä, A

doi:10.3891/acta.chem.scand.26-2713

Cited by 29 publications

(6 citation statements)

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“…Other studies (Huunan-Seppala, 1972) have suggested the existence of a binding process to phospholipids, similar to that reported by Balzer, Makinose, Fiehn & Hasselbach (1968) for various lipophilic amines: chlorpromazine, prenylamine, reserpine. The same hypothesis was invoked in the case of imipramine concentration in the lung (Junod, 1972a), and the interrelations between drugs of similar nature are consistent with that concept.…”

Section: Discussionsupporting

confidence: 52%

“…A similar observation was reported by Huunan-Seppala (1972) for binding of propranolol to mitochondria, by Kwant & Seeman (1969) for binding of chlorpromazine to red cells, by Balzer et al (1968) (1974) extended their studies on the nature of the concentration process of imipramine, amphetamine, chlorcyclizine and methadone. They were able to find evidence for the presence of two components of accumulation: a linear one and a saturable one, for high and low substrate concentrations respectively.…”

Section: Discussionsupporting

confidence: 48%

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Concentration of (±)‐propranolol in Isolated, Perfused Lungs of Rat

Dollery¹,

Junod²

1976

British J Pharmacology

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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 giM 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. IntroductionPrevious studies on the distribution of (±)propranolol in tissues have shown that the lungs were able to concentrate (±)-propranolol to a remarkable extent since a tissue/medium ratio of up to 250 was observed (Black, Duncan & Shanks, 1965). Further analysis (Hayes & Cooper, 1971) showed that in rats, dogs and monkeys, large amounts of metabolites of propranolol could also be detected in the lungs. It was not known if the presence of these metabolites was the result of the local pulmonary metabolism of propranolol or of their accumulation after production elsewhere in the body.The present studies were therefore undertaken to investigate the mechanism of concentration and the possible metabolism of (±)-propranolol in isolated perfused lungs of the rat. In view of their similar physicochemical properties, it was also interesting to compare the mode of accumulation of propranolol with that of imipramine and other basic amines, whose concentration in the lungs has already been the object of recent studies (Junod, 1972a, Andersen, Orton, Pickett & Eling, 1974 Iwasawa & Gillis (1974), propranolol had no effect on noradrenaline uptake by the lung. Methods Medium and materialsThe perfusion medium consisted of Krebs-Ringer bicarbonate buffer, containing 5 mM glucose and 4.5% bovine serum albumin; to obtain a Na+-free medium, sucrose was substituted for NaCl and Tris HCI for NaHCO3, while the albumin was made Na+-free according to the procedure already described (Junod, 1972b Unless otherwise specified, drugs were added to the perfusion medium and were therefore present during the entire perfusion. In the experiments where the effects of drugs on the efflux of propranolol were studied, drugs were added to the perfusion medium only during the period when efflux of 14C was measured. Experimental proceduresDetails of t...

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Section: Discussionsupporting

confidence: 52%

Section: Discussionsupporting

confidence: 48%

Concentration of (±)‐propranolol in Isolated, Perfused Lungs of Rat

Dollery¹,

Junod²

1976

British J Pharmacology

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“…Two independent sets of binding sites have been demonstrated for propranolol and chlorpromazine in isolated rat liver mitochondria (Huunan Seppala, 1972). Since both compounds competitively inhibit the uptake of HIPDM by the isolated-perfused rat lung (Slosman et a f .…”

Section: Discussionmentioning

confidence: 99%

Evaluation of non‐respiratory function of the human lung by HIPDM lung scanning

Miniati¹,

Cocci²,

Paci³

et al. 1992

Clinical Physiology

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“…The tetrodotoxin-insensitive component of veratridine-induced propranolol release may represent an interaction between veratridine and propranolol unrelated to depolarization, possibly a displacement of propranolol from membranes by the lipophilic veratridine molecule. Propranolol has been shown to bind to biological membranes and model membrane systems (Huunan-Seppala, 1972;Godin et al, 1976;Lee, 1977;Herbette et al, 1983) and membrane interactions between propranolol and other lipophilic amines have been demonstrated (Dollery & Junod, l976;Vestal et al, 1980;Hemsworth & Street, 1981;Rudnick et al, 1981).…”

Section: Discussionmentioning

confidence: 99%

Depolarization‐induced release of propranolol and atenolol from rat cortical synaptosomes

Bright¹,

Gaffney

Street³

et al. 1985

British J Pharmacology

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The accumulation and release of [3H]‐propranolol and [3H]‐atenolol were examined in synaptosomes from rat cerebral cortex. Synaptosomes accumulated 20 pmol propranolol and 0.6 pmol atenolol mg−1 protein when incubated at 30°C with radiolabeled drugs (0.1 μm). Exposure of propranolol‐loaded synaptosomes to elevated K+, Rb+ or Cs+ evoked a concentration‐dependent increase in propranolol efflux. The action of these ions in releasing propranolol was highly correlated with their ability to produce synaptosomal membrane depolarization, as estimated with the voltage‐sensitive dye diS‐C3‐(5). Elevated K+ also promoted atenolol release from synaptosomes in a concentration‐dependent manner. Veratridine (10 μm) released propranolol and atenolol from synaptosomes and these effects were antagonized by tetrodotoxin (1 μm). Under Ca2+‐free conditions, K+‐induced release of propranolol was reduced by 37% and atenolol release was diminished by 68%. The results support the concept that both polar and non‐polar β‐adrenoceptor blocking drugs may be accumulated by nerve endings for release by membrane depolarization and suggest that neural storage and release of these molecules may influence their concentrations at localized sites of action.

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Binding of Propranolol and Chlorpromazine by Mitochondrial Membranes.

Cited by 29 publications

References 0 publications

Concentration of (±)‐propranolol in Isolated, Perfused Lungs of Rat

Concentration of (±)‐propranolol in Isolated, Perfused Lungs of Rat

Evaluation of non‐respiratory function of the human lung by HIPDM lung scanning

Depolarization‐induced release of propranolol and atenolol from rat cortical synaptosomes

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