This study maps the binding sites of endothelin isoforms and related peptides in mammalian heart and kidney, suggesting the existence of multiple receptor subtypes with varying affinities.
Quantitative in vitro receptor autoradiography was used to identify and compare binding sites for endothelin-1 (ET-1), ET-2, and ET-3, mouse vasoactive intestinal contractor (VIC), and sarafotoxin S6b in human, porcine, and rat cardiac and renal tissues. In the rat kidney, the highest densities of binding sites for all five labeled peptides were present in the glomeruli, with lower levels in the papilla, cortex, and inner band of the medulla. A similar pattern was found in porcine and human kidney except that no discrete glomerular binding could be detected. In the heart, higher densities were detected in the atria compared to the ventricle. Although the pattern of binding in cardiac and renal tissue was similar for all four labeled ET isoforms, nonspecific binding was consistently higher with ET-3, resulting in lower levels of specific binding. These results suggest that these peptides could be acting via the same population of binding sites, but multiple receptor subtypes may exist that differ in their rank order of affinity for the ET isoforms and sarafotoxin S6b, as proposed in other tissues.
Davenport et al. (1991) studied this question.