SUMMARYIsolated guinea-pig lungs perfused with Krebs solution were found to remove 5-hydroxytryptamine (5HT) from the fluid perfusing them. Two processes were involved: (I) the active uptake of 5HT by cells in the lungs, and (2) the metabolism of 5HT to 5-hydroxyindole-acetic acid (5HIAA). The experiments emphasize that the lungs have a metabolic capacity in addition to their passive function of gas diffusion.Derangement of the metabolic functions of the lungs may prove to be as serious clinically as derangement of their respiratory functions. Failure to clear the venous plasma of free 5HT would affect the aggregation of platelets and might thus have a bearing on the problem of deep venous thrombosis in man.DESPITE their tenuous anatomical structure the lungs have a remarkable ability to affect substances 15-17 responsible for maintaining the low level of about 6 ng. per ml. of free 5HT that is normally found in human plasma (Genefke, Garel, and Mandel, 1968). A tenfold increase causes platelets to undergo reversible aggregation and accelerates the irreversible second stage of aggregation which is produced, for example, by adrenaline or adenosine diphosphate (Baumgartner and Born, 1968). These authors also showed that very high concentrations of 5HT have the opposite effect; they inhibit both stages of platelet aggregation. Since aggregating platelets release large amounts of 5HT they speculated that this substance plays an important role in haemostasis by promoting thrombus formation until bleeding stops and the 5HT is no longer washed away. The concentration of 5HT then builds up locally and inhibits further thrombosis. Correct functioning of this complex mechanism requires strict control of the free plasma 5HT by the lungs. It is possible that derangement of this mechanism might contribute to perfused through them. Examples are 5-hydroxytryptamine (5HT) and the prostaglandins; when these substances are infused intravenously into anaesthetized dogs very little of the infused activity appears in the arterial blood (Ferreira and Vane, 1967;Thomas and Vane, 1967 The heart and lungs were removed from freshly killed guinea-pigs weighing 0.5-1.2 kg. A polythene cannula was tied into the trachea to allow a few gentle inflations of the lungs; this helped to flush out blood when perfusion started. A second cannula was
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