Brain and atrial natriuretic peptides bind to common receptors in brain capillary endothelial cells.
The recent discovery of brain natriuretic peptides (BNP) that stimulates natriuresis, diuresis, and vascular smooth muscle relaxation in a manner similar to that of atrial natriuretic peptide (ANP) suggests the possibility that these endocrine hormones function via some common mechanism. Indirect evidence from several laboratories suggests that BNP and ANP may bind to the same receptors. We examined whether ANP and BNP bind to a common set of receptors in cultured bovine brain capillary endothelial cells and in bovine aortic endothelial cells. Scatchard plot analysis of binding data shows a similar dissociation constant (KD) of approximately 0.3 nM and a maximal binding capacity (Bmax) of 50 fmol/mg protein for both natriuretic peptides in brain capillary cells and 0.6 nM and 80 fmol/mg protein, respectively, in the aortic endothelial cells. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the affinity cross-linked receptor-ligand complex shows a strongly labeled 65-kDa receptor and a 125-kDa band that is likely to be a receptor of the guanylate cyclase type. ANP and BNP cross compete equally for binding to the two receptors identified on the gels. ANP and BNP also stimulate guanosine 3', 5'-cyclic monophosphate production in these cells, consistent with the presence of a functional guanylate cyclase-linked B receptor. We conclude that ANP and BNP share common receptors in brain capillary and aortic endothelial cells.
Department of Medicine, Long Beach Veterans Administration, California.
R A
RA
Gelfand
H J
HJ
Frank
E
E
Levin
A
A
Pedram
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000378:metabolism*; D001667:Binding, Competitive; D002196:Capillaries / Q000166:cytology / Q000378:metabolism; D002478:Cells, Cultured; D002560:Cerebrovascular Circulation; D003432:Cross-Linking Reagents; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D006162:Guanylate Cyclase / Q000378:metabolism; D020097:Natriuretic Peptide, Brain; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D017461:Receptors, Atrial Natriuretic Factor; D011956:Receptors, Cell Surface / Q000378:metabolism
D003432:Cross-Linking Reagents; D009419:Nerve Tissue Proteins; D011956:Receptors, Cell Surface; C058930:brain natriuretic peptide receptor; D020097:Natriuretic Peptide, Brain; D009320:Atrial Natriuretic Factor; D006162:Guanylate Cyclase; D017461:Receptors, Atrial Natriuretic Factor