Brain natriuretic peptide: interaction with renal ANP system.
Brain natriuretic peptide (BNP) has recently been found in porcine brain and has been shown to cause diuresis and natriuresis when injected in rats, effects similar to those caused by atrial natriuretic peptide (ANP). BNP is also synthesized in the cardiac atria and circulates in plasma. The amino acid sequence of the peptide resembles that of ANP particularly closely within the ring structure of the peptide. We examined the potential role of BNP in modulating renal function by assessing its ability to mimic the effects of ANP on rat glomeruli and in rabbit inner medullary collecting duct cells (IMCD). BNP bound with high affinity to glomeruli (Kd approximately 900 pM) and IMCD cells (Kd approximately 500 pM). In IMCD cells, BNP stimulated particulate guanylate cyclase (approximately 3-fold at maximum ligand concentration) and inhibited conductive 22Na+ uptake by 50% at concentrations at which ANP is also effective. In rat glomeruli, BNP bound with high affinity to the low-molecular-weight receptors but with lesser affinity to the higher-molecular-weight guanylate cyclase-linked receptors (Kd approximately 50 nM). In addition, the guanosine 3',5'-cyclic monophosphate accumulation response was less impressive in glomeruli than the guanylate cyclase response in IMCD tissue. Thus we conclude that BNP is of only slightly reduced affinity and potency for the ANP receptors in the kidney and probably acts through these receptors to exert its physiological effects.
Gunning
M
M
Department of Medicine, Brigham and Women's and Beth Israel Hospitals, Boston, Massachusetts.
Ballermann
B J
BJ
Silva
P
P
Brenner
B M
BM
Zeidel
M L
ML
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000378:metabolism / Q000502:physiology*; D006162:Guanylate Cyclase / Q000378:metabolism; D007668:Kidney / Q000378:metabolism*; D007678:Kidney Glomerulus / Q000378:metabolism; D007679:Kidney Medulla; D007685:Kidney Tubules, Collecting / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D008566:Membranes / Q000378:metabolism; D020097:Natriuretic Peptide, Brain; D009419:Nerve Tissue Proteins / Q000502:physiology*; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D017461:Receptors, Atrial Natriuretic Factor; D011956:Receptors, Cell Surface / Q000378:metabolism; D012964:Sodium / Q000378:metabolism
D009419:Nerve Tissue Proteins; D011956:Receptors, Cell Surface; D020097:Natriuretic Peptide, Brain; D009320:Atrial Natriuretic Factor; D012964:Sodium; D006162:Guanylate Cyclase; D017461:Receptors, Atrial Natriuretic Factor