Localization of Endothelin Binding Sites and Endothelin-Like Immunoreactivity in Human Fetal Heart

Abstract

The localization of [125I]endothelin-1 ([125I]ET-1) and [125I]endothelin-3 ([125I]ET-3) binding sites, as well as ET-like immunoreactivity, was investigated in sections of human fetal heart, using in vitro autoradiographic and immunohistochemical techniques. High-affinity [125I]ET-1 binding sites showed a tissue-specific distribution pattern, with high-density binding to the atria, ventricles (77-100 amol/mm2), and cardiac valve cusps (120.6 +/- 2.6 amol/mm2). Specific high-density binding of [125I]ET-3 was also exhibited on valve cusps (143.2 +/- 2 amol/mm2), whereas a much lower density of binding was displayed on atria and ventricles (10-15 amol/mm2). Microautoradiographic examination demonstrated binding sites on the wall of the aorta, pulmonary and coronary arteries, myocardium, ventricular conduction system, endocardium, and endothelial lining of valve cusps. Regional differences in the density and affinity of ET binding sites suggest that subpopulations of receptors are present in the human fetal heart. ET-like immunoreactivity was localized to a heterogeneous population of endothelial, endocardial, and epicardial mesothelial cells. The concordant localization of specific binding sites and ET-like immunoreactive cells indicates that locally released peptide might have a paracrine or autocrine role, possibly influencing cardiovascular development and function.