IDENTIFICATION OF [I-125] ENDOTHELIN BINDING-SITES IN HUMAN CORONARY TISSUE

In vitro receptor autoradiography has been used to study the distribution of [I-125]endothelin binding sites in human coronary tissue from patients undergoing cardiac transplantation. Dense binding of [I-125]endothelin was associated with the smooth muscle of epicardial coronary arteries as well as to perivascular regions of these vessels. Binding was also associated with the ventricular myocardium. There was an increased binding of [I-125]endothelin to atheromatous tissue, both coronary arteries and vein graft. The [I-125]endothelin binding sites identified using in vitro autoradiography are likely to be functionally relevant since endothelin causes a concentration-dependent contraction of segments of human epicardial coronary arteries in vitro and also has positive inotropic activity on isolated human cardiomyocytes. The presence of specific binding sites for [I-125]endothelin on coronary tissue and the increased binding in atheromatous tissue suggest that endothelin is a peptide which may play a role in the maintenance of vascular tone and/or the pathogenesis of ischaemic heart disease.