title: Endothelin receptors in the human coronary artery, ventricle and atrium. A quantitative autoradiographic analysis.
abstract: In the present experiments we investigated endothelin (ET) receptors in the human coronary artery, and in ventricular and atrial muscle using quantitative receptor autoradiography. Displacement of [125I]Sf6b (Sarafotoxin S6b) (30 pM)- and [125I]ET-1 (30 pM)-labeled binding sites was studied using ET-1, the ETA receptor selective ligand BQ-123 (cyclo[D-Asp-L-Pro-D-Val-L-Leu-D-Trp-]), and the ETB receptor selective ligand [Ala1, 3, 11, 15]ET-1. Specific binding was more dense in atrium and coronary artery (relative optical density (r.o.d.): 0.14 +/- 0.01 and 0.16 +/- 0.01, respectively) than in ventricular muscle (r.o.d.: 0.10 +/- 0.01). In the coronary artery, binding was especially dense in the media. ET-1 displaced [125I]ET-1 and [125I]Sf6b monophasically in atrium, ventricle and coronary artery. [Ala1,3,11,15]ET-1 and BQ-123 displaced [125I]ET-1 and [125I]Sf6b-labeled sites biphasically in the ventricle and in the atrium. In the human coronary artery, [Ala1,3,11,15]ET-1 and BQ-123 displaced [125I]ET-1-labeled sites monophasically (pIC50: ET-1 (9.72 +/- 0.12) > BQ-123 (6.84 +/- 0.08) > [Ala1,3,11,15]ET-1 (6.40 +/- 0.12). In contrast, [Ala1,3,11,15]ET-1 and BQ-123 displaced [125I]Sf6b-labeled coronary artery sites biphasically (high affinity pIC50: BQ-123, 9.03 +/- 0.25; [Ala1,3,11,15]ET-1, 8.40 +/- 0.14; low affinity pIC50: BQ-123, 7.24 +/- 0.14; [Ala1,3,11,15]ET-1, 6.99 +/- 0.09). These data indicate that both [125I]ET-1 and [125I] Sf6b-labeled ETA and ETB binding sites in human ventricular and atrial muscle.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Pharmacology, Faculty of Medicine and Health Sciences, Erasmus University Rotterdam, The Netherlands.
authors.forename: W A
authors.initials: WA
authors.lastname: Bax
authors.forename: A T
authors.initials: AT
authors.lastname: Bruinvels
authors.forename: R J
authors.initials: RJ
authors.lastname: van Suylen
authors.forename: P R
authors.initials: PR
authors.lastname: Saxena
authors.forename: D
authors.initials: D
authors.lastname: Hoyer
mesh_terms: D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D001345:Autoradiography; D001667:Binding, Competitive / Q000187:drug effects; D002648:Child; D003331:Coronary Vessels / Q000033:anatomy & histology / Q000378:metabolism*; D065128:Endothelin Receptor Antagonists; D005260:Female; D006321:Heart / Q000033:anatomy & histology; D006325:Heart Atria / Q000033:anatomy & histology / Q000378:metabolism; D006352:Heart Ventricles / Q000033:anatomy & histology / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D007457:Iodine Radioisotopes; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009206:Myocardium / Q000378:metabolism*; D010456:Peptides, Cyclic / Q000494:pharmacology; D017466:Receptors, Endothelin / Q000378:metabolism*; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014757:Viper Venoms / Q000494:pharmacology
chemical_list: D065128:Endothelin Receptor Antagonists; D007457:Iodine Radioisotopes; D010456:Peptides, Cyclic; D017466:Receptors, Endothelin; D014662:Vasoconstrictor Agents; D014757:Viper Venoms; C057354:sarafotoxins s6; C072247:cyclo(Trp-Asp-Pro-Val-Leu)