title: Identification of cardiac endothelin binding sites in rats: downregulation of left atrial endothelin binding sites in response to myocardial infarction.
abstract: Endothelin-1 (ET-1) is a recently described potent vasoconstrictor peptide. Plasma and myocardial tissue levels of ET-1 are increased following myocardial ischemia, however, the factors which regulate ET-1 binding sites in vivo are not well understood. ET-1 binding sites were measured by Scatchard analysis of [125I]ET-1 binding to membranes of rat myocardium. The highest number of ET-1 binding sites (2,951 fmol/mg protein) were found in right atrial tissue, and followed the rank order of right atrium greater than left atrium (2,157 fmol/mg protein), greater than right ventricle (835 fmol/mg protein), greater than septum (609 fmol/mg protein) = left ventricle (498 fmol/mg protein). Following coronary artery occlusion for 24 h, ET-1 binding sites of left atrium were decreased by 35% (p less than 0.01), without a change in the Kd (i.e., 98 pM). Other regions of the myocardium did not exhibit any change in the number of ET-1 binding sites. Similarly, no change in ET-1 binding sites were observed following coronary artery occlusion for 0.5 h followed by 24 h reperfusion. These data indicate that there exists considerable regional differences in the density of ET-1 binding sites in the myocardium, and that ET-1 sites are selectively reduced in left atrial tissue following myocardial infarction.
authors.affiliation: Department of Pharmacology, SmithKline Beecham Pharmaceuticals, King of Prussia, Pa.
authors.forename: P
authors.initials: P
authors.lastname: Nambi
authors.forename: M
authors.initials: M
authors.lastname: Pullen
authors.forename: J W
authors.initials: JW
authors.lastname: Egan
authors.forename: E F
authors.initials: EF
authors.lastname: Smith
mesh_terms: D000818:Animals; D015536:Down-Regulation / Q000502:physiology*; D016232:Endothelins / Q000378:metabolism*; D007457:Iodine Radioisotopes; D007700:Kinetics; D008297:Male; D009203:Myocardial Infarction / Q000378:metabolism*; D015428:Myocardial Reperfusion Injury / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface / Q000378:metabolism*; D017466:Receptors, Endothelin
chemical_list: D016232:Endothelins; D007457:Iodine Radioisotopes; D011956:Receptors, Cell Surface; D017466:Receptors, Endothelin