Receptor subtypes for vasonatrin peptide in renal glomeruli and arteries.
Vasonatrin peptide (VNP) is a synthetic new member of the natriuretic peptide family. VNP is a chimera of CNP and ANP, which possesses the 22-amino acid ringed structure of CNP and the COOH terminus of ANP. VNP shares properties with ANP and CNP but also shows functional characteristics distinct from those induced by the original natriuretic peptides. This study investigates VNP binding to specific sites in the kidney and femoral artery, in order to clarify the nature of the receptors through which VNP exerts its effects. Using autoradiographic techniques we have found that VNP binds to renal and arterial tissue sections. VNP binding was displaced by incubation in the presence of 1 microM ANP(1-28), CNP(1-22) and C-ANP, which suggests that VNP mostly binds to NPR-C. Cross-linking studies performed in rat glomerular membranes confirmed that VNP mainly binds to the 67 kDa-NPR-C-like protein and also to NPR-A. Consistent with this, our results indicate that VNP inhibits cAMP synthesis stimulated by the physiological agonist histamine in a concentration-dependent manner, without having any effect on basal cAMP production. Finally, we have found that VNP increases cGMP production in rat renal glomeruli, suggesting that this peptide functionally binds to NPR-A.
Woodard
Geoffrey E
GE
National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health (Building 10, Rm 8C-208), 10 Center Drive, MSC 1752 Bethesda, MD 20892, USA. GeoffreyW@intra.niddk.nih.gov
Li
Xiaohong
X
Brown
John
J
Rosado
Juan A
JA
D000818:Animals; D001158:Arteries / Q000166:cytology / Q000378:metabolism*; D009320:Atrial Natriuretic Factor / Q000378:metabolism / Q000494:pharmacology*; D001667:Binding, Competitive; D004285:Dogs; D006162:Guanylate Cyclase / Q000378:metabolism*; D007668:Kidney / Q000098:blood supply / Q000166:cytology / Q000378:metabolism*; D008297:Male; D009924:Organ Culture Techniques; D051381:Rats; D017208:Rats, Wistar; D017461:Receptors, Atrial Natriuretic Factor / Q000378:metabolism*; D012079:Renal Circulation / Q000187:drug effects / Q000502:physiology*
C068986:ventricular natriuretic peptide, eel; D009320:Atrial Natriuretic Factor; D006162:Guanylate Cyclase; D017461:Receptors, Atrial Natriuretic Factor; C091715:atrial natriuretic factor receptor A