Endothelin receptors in human placenta: relationship to vascular resistance and thromboxane release.
This investigation was performed to study the potential role of endothelin in the modulation of fetoplacental vascular resistance in the human placenta. Full-term placentas from uncomplicated pregnancies were studied within 30 min of delivery. The umbilical artery and vein to a single placental cotyledon were cannulated and the artery perfused with RPMI media (0.82 ml/min). Endothelin 1 caused a sustained dose-dependent increase in perfusion pressure. Infused endothelin 1 (50 nM) stimulated thromboxane release 2.3-fold compared with basal values. Thromboxane release persisted for 15 min after discontinuation of endothelin. Properties of human placental endothelin 1 receptors were defined in binding studies performed on a crude membrane fraction of placental cotyledons. 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 Kd of 36.1 +/- 9.7 pM and a density of 185.4 +/- 9.6 fmol/mg protein (n = 5). The potency order for competitive inhibition of the binding of 125I-labeled endothelin 1 was endothelin 1 greater than endothelin 2 = endothelin 3 = sarafotoxin S6b greater than big endothelin (human) = big endothelin (porcine). Phenylephrine, bradykinin, norepinephrine, atrial natriuretic factor, diltiazem, U46619, and angiotensin II did not displace 125I-endothelin 1 from its receptors. These experiments demonstrate that endothelin 1 is a potent pressor substance in the human fetoplacental cotyledon. Pressor effects of endothelin may be mediated by a combination of direct effects and stimulation of vasoconstrictor prostanoids.
Wilkes
B M
BM
Department of Medicine, North Shore University Hospital, Manhasset, New York.
Mento
P F
PF
Hollander
A M
AM
Maita
M E
ME
Sung
S
S
Girardi
E P
EP
D001667:Binding, Competitive; D002462:Cell Membrane / Q000378:metabolism; D016232:Endothelins; D004730:Endothelium, Vascular / Q000502:physiology; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D010455:Peptides / Q000378:metabolism / Q000494:pharmacology*; D010477:Perfusion; D010920:Placenta / Q000098:blood supply / Q000502:physiology*; D011247:Pregnancy; D011869:Radioligand Assay; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000502:physiology*; D017466:Receptors, Endothelin; D013929:Thromboxane B2 / Q000378:metabolism*; D014655:Vascular Resistance
D016232:Endothelins; D010455:Peptides; D011956:Receptors, Cell Surface; D017466:Receptors, Endothelin; D013929:Thromboxane B2