Characterization of binding sites in rat for A, B and C-type natriuretic peptides.
Binding studies, affinity cross-linking and guanylate cyclase assays allowed a comparison of receptors with which the rat forms of atrial/A-type natriuretic peptide (rANP), brain/B-type natriuretic peptide (rBNP) and C-type natriuretic peptide (rCNP) interact in rat kidney cortex and lung. This work represents the first study in which the rat form of BNP (= rBNP-45/iso-rANP(1-45)) has been used as a radiolabelled tracer to further characterize its receptors in these tissues. In addition, these studies stress the use of the same species of natriuretic peptide and assay system, an important experimental des ign given that BNPs show species-specific differences in structure. rBNP-45 bound with lower affinity to rANP (99-126) receptors, namely guanylate cyclase-linked receptor(s) and C-receptor. No receptor which interacted with only rBNP-45 was detectable in lung and kidney cortex. Since rBNP-45 interacted preferentially with the C-receptor and was less potent than rANP(99-126) in stimulating glomerular guanylate cyclase, rBNP-45 may signal through another second messenger in addition to cyclic GMP. Work with truncated analogues of this hormone pinpointed regions of this peptide which may contribute to receptor binding affinity and guanylate cyclase activation. CNP-22 bound to only a subset of ANP receptors and was least effective in stimulating glomerular guanylate cyclase, suggesting a differential mode of action from ANP.
Weir
M L
ML
Department of Biochemistry, Queen's University, Kingston, Canada.
Pang
S C
SC
Flynn
T G
TG
D000595:Amino Acid Sequence; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000378:metabolism*; D001665:Binding Sites; D001667:Binding, Competitive; D002462:Cell Membrane / Q000378:metabolism; D006162:Guanylate Cyclase / Q000378:metabolism; D007672:Kidney Cortex / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D008969:Molecular Sequence Data; D020097:Natriuretic Peptide, Brain; D020098:Natriuretic Peptide, C-Type; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D051381:Rats; D017461:Receptors, Atrial Natriuretic Factor / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D015398:Signal Transduction
D009419:Nerve Tissue Proteins; D011994:Recombinant Proteins; C058930:brain natriuretic peptide receptor; D020097:Natriuretic Peptide, Brain; D020098:Natriuretic Peptide, C-Type; D009320:Atrial Natriuretic Factor; D006162:Guanylate Cyclase; D017461:Receptors, Atrial Natriuretic Factor; C073616:atrial natriuretic factor receptor C