Atrial and brain natriuretic peptides share binding sites in the kidney and heart.
We examined the distribution of binding sites for atrial natriuretic peptide (ANP) and the recently discovered brain natriuretic peptide (BNP) in rat kidney and heart by receptor autoradiography. In frozen kidney sections, both 125I-ANP and 125I-BNP exhibited localized binding to cortical glomeruli. The binding of each radiolabeled peptide was abolished by inclusion of either excess (1 microM) unlabeled ANP or excess unlabeled BNP, suggesting that ANP and BNP share cortical glomerular binding sites. In frozen cardiac sections, ANP and BNP binding sites were localized to the endothelium of the endomural channels and endocardium. As was the case for kidney, binding of each peptide at these sites was abolished by the presence of excess unlabeled ANP or BNP, suggesting that these natriuretic peptides share binding sites in the heart as well. To explore further the possibility that ANP and BNP utilize the same receptor(s), we performed competitive binding experiments using cultured pulmonary artery endothelial (CPAE) cells. ANP and BNP competitively displaced one another with equivalent IC50 values from CPAE cell binding sites. Furthermore, both ANP and BNP elevated the levels of cGMP, a putative second messenger for ANP, in these cells. These data are consistent with the observation that BNP, like ANP, causes a natriuresis and diuresis in rats, and suggest that BNP may possess other biological activities known for ANP.
Oehlenschlager
W F
WF
Department of Molecular Pharmacology and Experimental Therapeutics, Medical University of South Carolina, Charleston 29425.
Baron
D A
DA
Schomer
H
H
Currie
M G
MG
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000378:metabolism*; D001345:Autoradiography; D001667:Binding, Competitive; D006152:Cyclic GMP / Q000378:metabolism; D004727:Endothelium / Q000166:cytology / Q000378:metabolism; D066298:In Vitro Techniques; D007457:Iodine Radioisotopes; D007668:Kidney / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D020097:Natriuretic Peptide, Brain; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D017461:Receptors, Atrial Natriuretic Factor; D011956:Receptors, Cell Surface / Q000378:metabolism*
D007457:Iodine Radioisotopes; D009419:Nerve Tissue Proteins; D011956:Receptors, Cell Surface; D020097:Natriuretic Peptide, Brain; D009320:Atrial Natriuretic Factor; D017461:Receptors, Atrial Natriuretic Factor; D006152:Cyclic GMP