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Palmitic acid-1-14C incorporation and turnover in lung phospholipids of rats treated with chlorphentermine, RMI 10.393 and Ro 4-4318

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Abstract

The effects of 3 lipidosis-inducing drugs on the incorporation and turnover of palmitic acid-1-14C in lung phospholipids was studied.

In rats treated with 1 dose of chlorphentermine or RMI 10.393, the incorporation of palmitate-1-14C into most lung phospholipid fractions was moderately decreased, but markedly lowered after 1 dose of Ro 4-4318.

Eight doses of chlorphentermine and RMI 10.393 strongly inhibited the incorporation of palmitate-1-14C into lung phospholipids, whereas with 8 doses of Ro 4-4318 the incorporation was highly increased.

Thirty hours after the last of 3 injections of the labeled palmitic acid the turnover of most lung phospholipids was considerably lower in chlorphentermine and RMI 10.393-treated rats than in controls. Ro 4-4318, however, induced a highly increased turnover of most phospholipids. After 54 h, this effect had practically disappeared.

Our studies showed that phospholipid storage after treatment with chlorphentermine and RMI 10.393 is mainly due to decreased degradation of phospholipids, whereas increased synthesis accounts for the effect of Ro 4-4318.

Zusammenfassung

An Ratten wurden die Wirkung von 3 Lipidose-erzeugenden Medikamenten auf den Einbau und den Turnover von Palmitinsäure-1-14C in Phospholipiden der Lunge untersucht.

Nach 1 Dosis Chlorphentermin und RMI 10.393 war der Einbau von Palmitinsäure-1-14C in die Lungenphospholipide leicht reduziert. Eine Dosis Ro 4-4318 dagegen führte zu stark vermindertem Palmitateinbau.

Acht Dosen Chlorphentermin und RMI 10.393 hemmten den Einbau von Palmitinsäure in die Lungenphospholipide deutlich. Acht Dosen Ro 4-4318 dagegen steigerten den Einbau von Palmitat in die einzelnen Phospholipidfraktionen.

Dreißig Stunden nach der letzten von 3 Palmitat-Injektionen war der Turnover der meisten Phospholipide in Chlorphentermin und RMI 10.393-behandelten Ratten niedriger als in Kontrollratten. Im Gegensatz dazu erhöhte Ro 4-4318 den Turnover der meisten Lungenphospholipide. Nach 54 Std hatte sich der Phospholipid-Turnover in den Rattenlungen weitgehend normalisiert.

Unsere Untersuchungen zeigten, daß die Phospholipidspeicherung, die durch Chlorphentermin und RMI 10.393 ausgelöst wird, auf einer Hemmung des Phospholipidabbaus zurückgeführt werden kann. Dagegen beruht die Phospholipidose, die durch Ro 4-4318 induziert wird, auf einer Aktivierung der Phospholipidsynthese.

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  1. Institute of Toxicology, Federal Institute of Technology and University of Zurich, Schorenstr. 16, CH-8063, Schwerzenbach, Switzerland

    D. Karabelnik & G. Zbinden

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  1. D. Karabelnik
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  2. G. Zbinden
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Karabelnik, D., Zbinden, G. Palmitic acid-1-14C incorporation and turnover in lung phospholipids of rats treated with chlorphentermine, RMI 10.393 and Ro 4-4318. Arch. Toxicol. 35, 163–174 (1976). https://doi.org/10.1007/BF00293563

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