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-(4-23) (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 (K(d)) 58 pM, maximum binding capacity (B(max)) 14 fmol/mg membrane protein, and K(d) 82 pM, B(max) 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 . 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.