title: Endothelin-1 conversion and receptor characterization in human placental arteries.
abstract: Endothelin-1-(1-21), a potent pressor peptide, is transcribed as big endothelin-(1-38) and converted to active peptide by endothelin-converting enzyme. The current investigation tested the hypothesis that human fetoplacental blood vessels convert big endothelin-1 to active peptide and that fetoplacental blood vessels respond to endothelin-1 by binding of the peptide to specific receptor sites. In the isolated perfused placental cotyledon the addition of big endothelin-1 to the perfusate caused a time-dependent increase in perfusion pressure that corresponded to the appearance of endothelin-1 in the perfusate. The properties of human placental endothelin-1 receptors were defined in binding studies performed on a plasma membrane fraction of small arteries (<1.0 mm) dissected from the placenta. Binding was saturable, reached steady state by 3 h at 25 degrees C, and was linear with protein concentration. Scatchard analysis of binding data indicated a single class of high-affinity binding sites with a dissociation constant of 27.6 +/- 2.3 pM and a density of 856 +/- 119 fmol/mg protein (n = 5). The potency order for competitive inhibition of the binding of 125I-labeled endothelin-1 [endothelin-1 = endothelin-2 > endothelin-3 = sarafotoxin S6b >> big endothelin-1 (human) = big endothelin-1 (porcine)] is most consistent with a type A endothelin receptor subtype. Phenylephrine, bradykinin, norepinephrine, atrial natriuretic factor, diltiazem, U-46619, and angiotensin II did not displace 125I-endothelin-1 binding. Endothelin receptors were shown to have an approximate molecular weight of 36,600 by polyacrylamide gel electrophoresis.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Medicine, North Shore University Hospital, Manhasset, New York.
authors.forename: B M
authors.initials: BM
authors.lastname: Wilkes
authors.forename: C M
authors.initials: CM
authors.lastname: Macica
authors.forename: P F
authors.initials: PF
authors.lastname: Mento
mesh_terms: D001158:Arteries / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D019332:Endothelin-1; D016232:Endothelins / Q000378:metabolism*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008970:Molecular Weight; D010477:Perfusion; D010920:Placenta / Q000098:blood supply*; D011247:Pregnancy; D011498:Protein Precursors / Q000378:metabolism; D017466:Receptors, Endothelin / Q000737:chemistry / Q000378:metabolism*
chemical_list: D019332:Endothelin-1; D016232:Endothelins; D011498:Protein Precursors; D017466:Receptors, Endothelin