Evidence for functional thromboxane A2-prostaglandin H2 receptors in human placenta.
The aim of this investigation was to study the role of thromboxane (TX) A2 in the modulation of human fetoplacental vascular resistance. By use of the isolated perfused fetoplacental cotyledon, TX generation (measured by direct radioimmunoassay of TXB2) was demonstrated on the fetal side of the placental circulation. The stable TX mimetic U-46619 caused a dose-dependent increase in perfusion pressure that was inhibited by the TX receptor antagonist SQ 29548. To further characterize the putative TXA2-prostaglandin H2 receptors, binding studies were performed in placental membranes using [3H]SQ 29548. Kinetic analysis revealed rapid and reversible specific binding of [3H]SQ 29548. Saturation binding and Scatchard analysis indicated radioligand binding to a single class of receptors (dissociation constant, 9.11 +/- 0.60 nM; receptor density, 103 +/- 8 fmol/mg protein, n = 4). Prostaglandins D2, E1, E2, F2a, and I2 did not inhibit the specific binding of [3H]SQ 29548 at concentrations less than or equal to 10 microM. This study demonstrates that the human placenta produces and releases TXA2, which can act locally via specific receptor sites to constrict the fetoplacental vasculature.
Hedberg
A
A
Department of Pharmacology, Squibb Institute for Medical Research, Princeton, New Jersey 08543-4000.
Mento
P F
PF
Liu
E C
EC
Hollander
A M
AM
Wilkes
B M
BM
D001667:Binding, Competitive; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002462:Cell Membrane / Q000378:metabolism; D005231:Fatty Acids, Unsaturated; D005260:Female; D006801:Humans; D006834:Hydrazines / Q000378:metabolism; D066298:In Vitro Techniques; D007700:Kinetics; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D011449:Prostaglandin Endoperoxides / Q000378:metabolism*; D011463:Prostaglandins H / Q000378:metabolism*; D011982:Receptors, Prostaglandin / Q000378:metabolism*; D017482:Receptors, Thromboxane; D044244:Receptors, Thromboxane A2, Prostaglandin H2; D013928:Thromboxane A2 / Q000037:antagonists & inhibitors / Q000378:metabolism*
D019086:Bridged Bicyclo Compounds, Heterocyclic; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines; D011449:Prostaglandin Endoperoxides; D011463:Prostaglandins H; D011982:Receptors, Prostaglandin; D017482:Receptors, Thromboxane; D044244:Receptors, Thromboxane A2, Prostaglandin H2; D013928:Thromboxane A2; C045749:SQ 29548