Aprotinin blocks the binding of pro atrial natriuretic peptides 1 to 30, 31 to 67, and 99 to 126 to human placental membranes.
Two peptides with natriuretic and diuretic properties consisting of amino acids 1 to 30 and 31 to 67 of the 98 amino acid N-terminal end of the prohormone of atrial natriuretic factor, which normally circulates in humans, were investigated to determine if they have specific binding sites of placental membranes. Competitive binding experiments revealed that atrial natriuretic peptides 1 to 30, 31 to 67, and 99 to 126 (i.e., C-terminus) each had specific and separate binding sites. The dissociation constants for atrial natriuretic peptides 1 to 30, 31 to 67, and 99 to 126 binding to human placental membranes were similar at 4.3 +/- 0.6 nmol/L, 3.1 +/- 0.4 nmol/L, and 2.9 +/- 0.5 nmol/L, respectively. Each peptide bound to the placental membranes between 10(-8) and 10(-11) mol/L but could bind to the other peptides' receptors only at supraphysiologic concentrations of 10(-6) and 10(-7) mol/L. The protease inhibitor aprotinin (50 micrograms/ml) blocked the binding of the atrial natriuretic peptides 1 to 30, 31 to 67, and 99 to 126 to their respective receptors. These results suggest that atrial natriuretic peptides 1 to 30 and 31 to 67 do not work through the atrial natriuretic factor receptor but rather have their own separate and distinct receptors on placental membranes and that the protease inhibitor aprotinin antagonizes their respective binding to placental membranes, suggesting that integral membrane proteases may be modulators of atrial natriuretic peptides receptor function.
Vesely
D L
DL
Department of Medicine, University of South Florida for Health Sciences, Tampa.
D007611:Aprotinin / Q000494:pharmacology*; D009320:Atrial Natriuretic Factor / Q000378:metabolism*; D001665:Binding Sites; D002462:Cell Membrane / Q000378:metabolism; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007457:Iodine Radioisotopes; D010446:Peptide Fragments / Q000378:metabolism; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D011498:Protein Precursors / Q000378:metabolism*
D007457:Iodine Radioisotopes; D010446:Peptide Fragments; D011498:Protein Precursors; D009320:Atrial Natriuretic Factor; D007611:Aprotinin