Clearance mechanisms of atrial and brain natriuretic peptides in rats.
To assess clearance mechanisms of atrial and brain natriuretic peptides in the circulation, we examined the effects of a neutral endopeptidase (NEP) inhibitor and a clearance receptor ligand on plasma concentrations of the peptides in normal rats. Plasma concentrations of endogenous alpha-rat atrial natriuretic peptide (alpha-rANP) were not significantly elevated by intravenous infusion of a NEP inhibitor, phosphoramidon, but were elevated threefold by intravenous infusion of a clearance receptor ligand, des(Gln18-Gly22)-rANP(4-23)-NH2 [C-ANF(4-23)]. On the other hand, the clearance of alpha-rANP given intravenously at the pharmacological dose, 600 pmol/min/kg for 2 min, was decreased to one-third by the administration of phosphoramidon, although the administration of C-ANF(4-23) did not significantly decrease the clearance. The clearance of rat brain natriuretic peptide (rBNP) given at 600 pmol/min/kg for 2 min was approximately 38% lower than that of alpha-rANP. The effect of phosphoramidon on the clearance of rBNP was not significant and was similar to that of C-ANF(4-23). These results suggest that clearance receptor is involved in the clearance of the physiological levels of alpha-rANP and that NEP plays a major role in the clearance of a pharmacological dose of alpha-rANP, at which clearance receptors are thought to be saturated, and also indicate a pharmacokinetic difference between alpha-rANP and rBNP.
Hashimoto
Y
Y
Department of Pharmacy, Kyoto University Hospital, Japan.
Nakao
K
K
Hama
N
N
Imura
H
H
Mori
S
S
Yamaguchi
M
M
Yasuhara
M
M
Hori
R
R
D000595:Amino Acid Sequence; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000097:blood / Q000493:pharmacokinetics*; D001798:Blood Proteins / Q000378:metabolism; D002417:Cattle; D006020:Glycopeptides / Q000494:pharmacology; D006801:Humans; D008297:Male; D008871:Microvilli / Q000378:metabolism; D008969:Molecular Sequence Data; D020097:Natriuretic Peptide, Brain; D015260:Neprilysin / Q000037:antagonists & inhibitors; D009419:Nerve Tissue Proteins / Q000097:blood / Q000493:pharmacokinetics*; D010446:Peptide Fragments / Q000097:blood / Q000493:pharmacokinetics*; D011485:Protein Binding; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000493:pharmacokinetics
D001798:Blood Proteins; D006020:Glycopeptides; D009419:Nerve Tissue Proteins; D010446:Peptide Fragments; D011994:Recombinant Proteins; C065367:atrial natriuretic factor (4-23)NH2, de-Gln(18)-de-Ser(19)-de-Gly(20,22)-de-Leu(21)-; D020097:Natriuretic Peptide, Brain; D009320:Atrial Natriuretic Factor; D015260:Neprilysin; C008890:phosphoramidon