γ-Atrial natriuretic polypeptide (γANP)-derived peptides in human plasma: Cosecretion of N-terminal γANP fragment and αANP

Hiroshi Itoh, K. Nakao, A. Sugawara, Y. Saito, M. Mukoyama, N. Morii, T. Yamada, S. Shiono, H. Arai, K. Hosoda, H. Imura

Research output: Contribution to journalArticle

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Abstract

Using RIAs for the N- and C-terminal fragments of the human atrial natriuretic polypeptide (ANP) precursor γANP, that is γANP-(1-25), and αANP [γANP-(99-126)], we studied the secretion of γANP-derived peptides from the heart in normal subjects and patients with heart disease, chronic renal failure, and cirrhosis. We detected γANP-(1-25)-like immunoreactivity (-LI) in plasma from normal subjects (n = 17) in considerable amounts [mean, 510 ± 62 (±SE) pg/mL (174 ± 21 pmol/L)]; the mean plasma αANP-LI level at the same time in these subjects was 32.8 ± 4.4 pg/mL (10.7 ± 1.4 pmol/L). Gel permeation chromatographic analysis of plasma samples from normal subjects and patients with heart disease and chronic renal failure revealed two major components; one was αANP, and the other was the 10K N-terminal γANP fragment (N-peptide) resulting from the removal of αANP (3K) from γANP (13K). In addition, γANP (13K), which possessed both γANP-(1-25)-LI and αANP-LI, and βANP, an antiparallel dimer of αANP, were detected in some patients as minor components. A significant positive correlation between plasma levels of the N-terminal γANP fragment and αANP (P < 0.01) and almost equal step-ups in the coronary sinusu plasma levels of the N-terminal γANP fragment and αANP suggest that they are cosecreted in equimolar amounts. The high molar ratio of plasma γANP-(1-25)-LI to αANP-LI (17.4 ± 1.4) in normal subjects and the significantly higher ratio in patients with chronic renal failure (36.9 ± 7.1; P < 0.01) suggest the slower clearance of the N-terminal γANP fragment than αANP and a role for the kidney in its degradation. Since the molar ratio of plasma γANP-(1-25)-LI to αANP-LI in patients with cirrhosis (20.7 ± 2.7) was similar to that in normal subjects, it is unlikely that the N-terminal γANP fragment is metabolized by the liver. In patients with heart disease, plasma γANP-(1-25)-LI and αANP-LI levels were higher in those with cardiac decompensation and were positively correlated with right atrial pressure, pulmonary arterial pressure, and pulmonary capillary wedge pressure, indicating cosecretion of the N-terminal γANP fragment and αANP in response to atrial stretch. The molar ratio of plasma γANP-(1-25)-LI to αANP-LI in patients with severe congestive heart failure (8.0 ± 1.2) was significantly lower than that in normal subjects (P < 0.05), suggesting an alteration in the secretion and/or metabolism of γANP-derived peptides in these patients. These results indicate that the simultaneous determination of the plasma levels of the N-terminal γANP fragment and αANP would serve as a clinical indicator of cardiac or renal function and possess potential usefulness for detecting abnormalities in the structure, secretion, and metabolic clearance of ANP.

Original languageEnglish
Pages (from-to)429-437
Number of pages9
JournalJournal of Clinical Endocrinology and Metabolism
Volume67
Issue number3
Publication statusPublished - 1988
Externally publishedYes

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Plasma (human)
Peptides
Plasmas
Chronic Kidney Failure

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

Cite this

γ-Atrial natriuretic polypeptide (γANP)-derived peptides in human plasma : Cosecretion of N-terminal γANP fragment and αANP. / Itoh, Hiroshi; Nakao, K.; Sugawara, A.; Saito, Y.; Mukoyama, M.; Morii, N.; Yamada, T.; Shiono, S.; Arai, H.; Hosoda, K.; Imura, H.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 67, No. 3, 1988, p. 429-437.

Research output: Contribution to journalArticle

Itoh, H, Nakao, K, Sugawara, A, Saito, Y, Mukoyama, M, Morii, N, Yamada, T, Shiono, S, Arai, H, Hosoda, K & Imura, H 1988, 'γ-Atrial natriuretic polypeptide (γANP)-derived peptides in human plasma: Cosecretion of N-terminal γANP fragment and αANP', Journal of Clinical Endocrinology and Metabolism, vol. 67, no. 3, pp. 429-437.
Itoh, Hiroshi ; Nakao, K. ; Sugawara, A. ; Saito, Y. ; Mukoyama, M. ; Morii, N. ; Yamada, T. ; Shiono, S. ; Arai, H. ; Hosoda, K. ; Imura, H. / γ-Atrial natriuretic polypeptide (γANP)-derived peptides in human plasma : Cosecretion of N-terminal γANP fragment and αANP. In: Journal of Clinical Endocrinology and Metabolism. 1988 ; Vol. 67, No. 3. pp. 429-437.
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abstract = "Using RIAs for the N- and C-terminal fragments of the human atrial natriuretic polypeptide (ANP) precursor γANP, that is γANP-(1-25), and αANP [γANP-(99-126)], we studied the secretion of γANP-derived peptides from the heart in normal subjects and patients with heart disease, chronic renal failure, and cirrhosis. We detected γANP-(1-25)-like immunoreactivity (-LI) in plasma from normal subjects (n = 17) in considerable amounts [mean, 510 ± 62 (±SE) pg/mL (174 ± 21 pmol/L)]; the mean plasma αANP-LI level at the same time in these subjects was 32.8 ± 4.4 pg/mL (10.7 ± 1.4 pmol/L). Gel permeation chromatographic analysis of plasma samples from normal subjects and patients with heart disease and chronic renal failure revealed two major components; one was αANP, and the other was the 10K N-terminal γANP fragment (N-peptide) resulting from the removal of αANP (3K) from γANP (13K). In addition, γANP (13K), which possessed both γANP-(1-25)-LI and αANP-LI, and βANP, an antiparallel dimer of αANP, were detected in some patients as minor components. A significant positive correlation between plasma levels of the N-terminal γANP fragment and αANP (P < 0.01) and almost equal step-ups in the coronary sinusu plasma levels of the N-terminal γANP fragment and αANP suggest that they are cosecreted in equimolar amounts. The high molar ratio of plasma γANP-(1-25)-LI to αANP-LI (17.4 ± 1.4) in normal subjects and the significantly higher ratio in patients with chronic renal failure (36.9 ± 7.1; P < 0.01) suggest the slower clearance of the N-terminal γANP fragment than αANP and a role for the kidney in its degradation. Since the molar ratio of plasma γANP-(1-25)-LI to αANP-LI in patients with cirrhosis (20.7 ± 2.7) was similar to that in normal subjects, it is unlikely that the N-terminal γANP fragment is metabolized by the liver. In patients with heart disease, plasma γANP-(1-25)-LI and αANP-LI levels were higher in those with cardiac decompensation and were positively correlated with right atrial pressure, pulmonary arterial pressure, and pulmonary capillary wedge pressure, indicating cosecretion of the N-terminal γANP fragment and αANP in response to atrial stretch. The molar ratio of plasma γANP-(1-25)-LI to αANP-LI in patients with severe congestive heart failure (8.0 ± 1.2) was significantly lower than that in normal subjects (P < 0.05), suggesting an alteration in the secretion and/or metabolism of γANP-derived peptides in these patients. These results indicate that the simultaneous determination of the plasma levels of the N-terminal γANP fragment and αANP would serve as a clinical indicator of cardiac or renal function and possess potential usefulness for detecting abnormalities in the structure, secretion, and metabolic clearance of ANP.",
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TY - JOUR

T1 - γ-Atrial natriuretic polypeptide (γANP)-derived peptides in human plasma

T2 - Cosecretion of N-terminal γANP fragment and αANP

AU - Itoh, Hiroshi

AU - Nakao, K.

AU - Sugawara, A.

AU - Saito, Y.

AU - Mukoyama, M.

AU - Morii, N.

AU - Yamada, T.

AU - Shiono, S.

AU - Arai, H.

AU - Hosoda, K.

AU - Imura, H.

PY - 1988

Y1 - 1988

N2 - Using RIAs for the N- and C-terminal fragments of the human atrial natriuretic polypeptide (ANP) precursor γANP, that is γANP-(1-25), and αANP [γANP-(99-126)], we studied the secretion of γANP-derived peptides from the heart in normal subjects and patients with heart disease, chronic renal failure, and cirrhosis. We detected γANP-(1-25)-like immunoreactivity (-LI) in plasma from normal subjects (n = 17) in considerable amounts [mean, 510 ± 62 (±SE) pg/mL (174 ± 21 pmol/L)]; the mean plasma αANP-LI level at the same time in these subjects was 32.8 ± 4.4 pg/mL (10.7 ± 1.4 pmol/L). Gel permeation chromatographic analysis of plasma samples from normal subjects and patients with heart disease and chronic renal failure revealed two major components; one was αANP, and the other was the 10K N-terminal γANP fragment (N-peptide) resulting from the removal of αANP (3K) from γANP (13K). In addition, γANP (13K), which possessed both γANP-(1-25)-LI and αANP-LI, and βANP, an antiparallel dimer of αANP, were detected in some patients as minor components. A significant positive correlation between plasma levels of the N-terminal γANP fragment and αANP (P < 0.01) and almost equal step-ups in the coronary sinusu plasma levels of the N-terminal γANP fragment and αANP suggest that they are cosecreted in equimolar amounts. The high molar ratio of plasma γANP-(1-25)-LI to αANP-LI (17.4 ± 1.4) in normal subjects and the significantly higher ratio in patients with chronic renal failure (36.9 ± 7.1; P < 0.01) suggest the slower clearance of the N-terminal γANP fragment than αANP and a role for the kidney in its degradation. Since the molar ratio of plasma γANP-(1-25)-LI to αANP-LI in patients with cirrhosis (20.7 ± 2.7) was similar to that in normal subjects, it is unlikely that the N-terminal γANP fragment is metabolized by the liver. In patients with heart disease, plasma γANP-(1-25)-LI and αANP-LI levels were higher in those with cardiac decompensation and were positively correlated with right atrial pressure, pulmonary arterial pressure, and pulmonary capillary wedge pressure, indicating cosecretion of the N-terminal γANP fragment and αANP in response to atrial stretch. The molar ratio of plasma γANP-(1-25)-LI to αANP-LI in patients with severe congestive heart failure (8.0 ± 1.2) was significantly lower than that in normal subjects (P < 0.05), suggesting an alteration in the secretion and/or metabolism of γANP-derived peptides in these patients. These results indicate that the simultaneous determination of the plasma levels of the N-terminal γANP fragment and αANP would serve as a clinical indicator of cardiac or renal function and possess potential usefulness for detecting abnormalities in the structure, secretion, and metabolic clearance of ANP.

AB - Using RIAs for the N- and C-terminal fragments of the human atrial natriuretic polypeptide (ANP) precursor γANP, that is γANP-(1-25), and αANP [γANP-(99-126)], we studied the secretion of γANP-derived peptides from the heart in normal subjects and patients with heart disease, chronic renal failure, and cirrhosis. We detected γANP-(1-25)-like immunoreactivity (-LI) in plasma from normal subjects (n = 17) in considerable amounts [mean, 510 ± 62 (±SE) pg/mL (174 ± 21 pmol/L)]; the mean plasma αANP-LI level at the same time in these subjects was 32.8 ± 4.4 pg/mL (10.7 ± 1.4 pmol/L). Gel permeation chromatographic analysis of plasma samples from normal subjects and patients with heart disease and chronic renal failure revealed two major components; one was αANP, and the other was the 10K N-terminal γANP fragment (N-peptide) resulting from the removal of αANP (3K) from γANP (13K). In addition, γANP (13K), which possessed both γANP-(1-25)-LI and αANP-LI, and βANP, an antiparallel dimer of αANP, were detected in some patients as minor components. A significant positive correlation between plasma levels of the N-terminal γANP fragment and αANP (P < 0.01) and almost equal step-ups in the coronary sinusu plasma levels of the N-terminal γANP fragment and αANP suggest that they are cosecreted in equimolar amounts. The high molar ratio of plasma γANP-(1-25)-LI to αANP-LI (17.4 ± 1.4) in normal subjects and the significantly higher ratio in patients with chronic renal failure (36.9 ± 7.1; P < 0.01) suggest the slower clearance of the N-terminal γANP fragment than αANP and a role for the kidney in its degradation. Since the molar ratio of plasma γANP-(1-25)-LI to αANP-LI in patients with cirrhosis (20.7 ± 2.7) was similar to that in normal subjects, it is unlikely that the N-terminal γANP fragment is metabolized by the liver. In patients with heart disease, plasma γANP-(1-25)-LI and αANP-LI levels were higher in those with cardiac decompensation and were positively correlated with right atrial pressure, pulmonary arterial pressure, and pulmonary capillary wedge pressure, indicating cosecretion of the N-terminal γANP fragment and αANP in response to atrial stretch. The molar ratio of plasma γANP-(1-25)-LI to αANP-LI in patients with severe congestive heart failure (8.0 ± 1.2) was significantly lower than that in normal subjects (P < 0.05), suggesting an alteration in the secretion and/or metabolism of γANP-derived peptides in these patients. These results indicate that the simultaneous determination of the plasma levels of the N-terminal γANP fragment and αANP would serve as a clinical indicator of cardiac or renal function and possess potential usefulness for detecting abnormalities in the structure, secretion, and metabolic clearance of ANP.

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