Characterization of atrial natriuretic peptide receptors in human fetoplacental vasculature.
Two classes of high-affinity binding sites for atrial natriuretic peptide (ANP) were identified in a microsomal fraction from human placental artery using radioligand binding methods and des[Gln18,Ser19,Gly20,Leu21,Gly22]ANP-(4-2 3) (C-ANP), a partially ring-deleted analogue of ANP, consistent with the presence of ANP-A and ANP-C receptor subtypes in this tissue [dissociation equilibrium constant (Kd) 58 pM, maximum binding capacity (Bmax) 14 fmol/mg membrane protein, and Kd 82 pM, Bmax 28 fmol/mg, respectively]. ANP activated a guanylate cyclase present in a particulate fraction from placental vascular tissue with half-maximal response at 104 pM and a maximal rate of guanosine 3',5'-cyclic monophosphate production of 62 pmol.min-1 x mg protein-1. Human brain natriuretic peptide was 10-fold less effective than ANP in stimulating guanylate cyclase activity, indicating the absence of the ANP-B receptor subtype. C-ANP had no effect on basal or ANP-stimulated enzyme activity. This report demonstrates the presence of functional (guanylate cyclase-coupled) receptors for ANP in the human fetoplacental vasculature, suggesting that ANP may have a role in the regulation of fetoplacental hemodynamics.
McQueen
J
J
Medical Research Council Blood Pressure Unit, Western Infirmary, Glasgow, Scotland, United Kingdom.
Kingdom
J C
JC
Whittle
M J
MJ
Connell
J M
JM
D015720:5'-Nucleotidase / Q000378:metabolism; D001158:Arteries / Q000648:ultrastructure; D009320:Atrial Natriuretic Factor / Q000378:metabolism / Q000494:pharmacology; D001667:Binding, Competitive; D006152:Cyclic GMP / Q000096:biosynthesis; D005333:Fetus / Q000098:blood supply*; D006162:Guanylate Cyclase / Q000378:metabolism; D006801:Humans; D007457:Iodine Radioisotopes; D007700:Kinetics; D008861:Microsomes / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology; D010920:Placenta / Q000098:blood supply*; D017461:Receptors, Atrial Natriuretic Factor / Q000378:metabolism*
D007457:Iodine Radioisotopes; D010446:Peptide Fragments; D009320:Atrial Natriuretic Factor; D015720:5'-Nucleotidase; D006162:Guanylate Cyclase; D017461:Receptors, Atrial Natriuretic Factor; D006152:Cyclic GMP