The fate of radioiodinated endothelin-1 and endothelin-3 in the rat

Abstract

Endothelin-1 (ET-1) has been isolated from cultured endothelial cells and might have a role in cardiovascular regulation. To study the fate of labeled ET-1, we prepared [125I]-labeled ET-1 (formerly porcine and human ET) and ET-3 (formerly rat ET). Approximately 0.2 microCi (0.2 pmol) was injected into the left ventricle of anesthetized rats and blood samples analyzed for radioactivity for up to 40 min. The animals were then killed and the distribution of radioactivity determined in various organs. Both ET-1 and ET-3 were rapidly removed from the circulation, with more than 60% of the removal occurring in the first minute. Removal of ET-1 was somewhat faster than that of ET-3. The highest uptake of radioactivity was seen in lung, kidney, and liver. When ET-1 was infused into the isolated perfused lung of the guinea pig, 64 +/- 1.9% of the label was retained. Subcellular fractionation of the lung homogenate following infusion of labeled ET-1 showed that 93% of the label was associated with membranes and intracellular organelles, suggesting internalization of the bound ET-1. Together, the results indicate a high density of ET-1 binding sites in the lung, liver, and kidney and that these organs may be important in removing circulating ET-1.