Metabolism of Sulfidopeptide Leukotrienes
Until recently there has been very little known about the ultimate metabolitc fate of the sulfidopeptide leukotrienes. A basic principle of the pharmacology of mediator substances requires that mechanisms exist for biological inactivation of these very potent molecules. One such mechanism might be simple uptake of leukotrienes by the cells which make or respond to them. Studies showing that LTC4, produced in the isolated perfused lung in response to the calcium ionophore A23187, was largely retained by the lung over a span of 10 minutes, and that very little conversion to LTD4/LTE4 took place, suggesting the possibility that a reuptake mechanism for LTC4 in the lung existed (1). Other eicosanoids (LTB4, 6-keto-PGF1, thromboxane B2 and PGE2) were largely released into the perfusate. It is also possible that LTC4 was retained through binding to tissue proteins with high affinity and not taken up into cells. Since direct experiments have now shown that leukotrienes are not stored in cells from which they are released, and, while the retention of LTC4 by the isolated perfused rat lung has not been fully explained, simple reuptake of LTC4 in the lung seems unlikely. At present it is thought that metabolic biotransformation is the primary mechanism of inactivation of the leukotrienes.
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