Partial Chemical Characterization of a Natriuretic Substance in Rat Atrial Heart Tissue

Trippodo, N. C.; MacPhee, Allan A.; Cole, Francis E.; Blakesley, Howard L.

doi:10.3181/00379727-170-41465

Cited by 69 publications

(38 citation statements)

References 4 publications

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“…Recently, a number of peptides with potent natriuretic, diuretic (1)(2)(3)(4)(5)(6)(7), and vasorelaxant activities (8)(9)(10) have been isolated from mammalian atria. Mammalian atrial cardiocytes contain specific granules which morphologically resemble those found in peptidesecreting cells (I 1).…”

Section: Introductionmentioning

confidence: 99%

Effect of atrial peptides on aldosterone production.

Atarashi¹,

Mulrow²,

Franco‐Saenz³

1985

J. Clin. Invest.

153

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This study examines the effects of the synthetic atrial peptides (atriopeptin I, II, and III) on aldosterone and corticosterone production by rat adrenal cell suspensions. Furthermore, we studied the effect of atriopeptin II infusion on the plasma aldosterone response to angiotensin II in the rat in vivo. Atriopeptin I, II, and III decreased aldosterone release from zona glomerulosa cells in a dose-dependent fashion. 10 pM atriopeptin II inhibited basal aldosterone release significantly (P < 0.01), and 10 nM atriopeptin II or III lowered it by 79%. Atriopeptin II decreased the sensitivity of the glomerulosa cells to adrenocorticotropic hormone (ACTH) and angiotensin II. Atriopeptin II had no effect on basal or ACTH-stimulated corticosterone release by fasciculata-medullary cells.In vivo infusions of angiotensin II with or without simultaneous infusions of atriopeptin II showed that atriopeptin II significantly inhibited the aldosterone response to angiotensin II. This inhibition by atriopeptin II was independent of any effect on plasma renin activity, serum potassium, or ACITH.These data raise the possibility that the atrial natriuretic peptides may affect sodium excretion by the kidney, not only directly, but also indirectly through the inhibition of aldosterone production.

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Section: Introductionmentioning

confidence: 99%

Effect of atrial peptides on aldosterone production.

Atarashi¹,

Mulrow²,

Franco‐Saenz³

1985

J. Clin. Invest.

153

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“…In recent years, efforts have been devoted to the purification and chemical characterization of ANF in the atrial muscle of the rat and other mammals (4)(5)(6)(7). However, these studies have been hampered by the scarcity of material available from rat atrial homogenates and also by the apparent heterogeneity of the biologically active factor (4,(7)(8)(9).…”

mentioning

confidence: 99%

Amino acid sequence of homologous rat atrial peptides: natriuretic activity of native and synthetic forms.

Seidah¹,

Lazure²,

Chrétien³

et al. 1984

Proc. Natl. Acad. Sci. U.S.A.

184

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A substance called atrial natriuretic factor (ANF), localized in secretory granules of atrial cardiocytes, was isolated as four homologous natriuretic peptides from homogenates of rat atria. The complete sequence of the longest form showed that it is composed of 33 amino acids. The three other shorter forms (2-33, 3-33, and 8-33) represent aminoterminally truncated versions of the 33 amino acid parent molecule as shown by analysis of sequence, amino acid composition, or both. The proposed primary structure agrees entirely with the amino acid composition and reveals no significant sequence homology with any known protein or segment of protein. The short form ANF-(8-33) was synthesized by a multifragment condensation approach and the synthetic product was shown to exhibit specific activity comparable to that of the natural ANF-(3-33).

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“…NatL Acad ScL USA 81 (1984) erated by trypsin treatment of the high molecular weight fraction correspond to the low molecular weight peptides obtained during our extraction procedure. One possibility is that the peptide(s) may exist in the atrial granules in the high molecular weight form and that our efforts (7) and those of others (4)(5)(6) to extract the peptides either with heat or acid (4-7) result in the proteolytic cleavage that induce the formation of the smaller peptide fraction. The high molecular weight peptide(s) may be either the post-translational precursor form(s) of the active peptide (e.g., prohormone) or the secreted form of the peptide, which is processed and activated at some other site(s).…”

Section: Discussionmentioning

confidence: 99%

“…The contents and function of granules located in mammalian cardiac atria remain to be established. A possible homeostatic function is implied by the demonstration that atrial stretch or myocardial volume overload cause a natriuresis and diuresis (3) and that atrial (but not ventricular) extracts possess natriuretic and diuretic activity when administered to rats (4)(5)(6). Partial purification of the atrial extract indicates the presence of several fractions with natriuretic activity (5,6).…”

mentioning

confidence: 99%

Proteolytic activation of a bioactive cardiac peptide by in vitro trypsin cleavage.

Currie¹,

Geller²,

Cole³

et al. 1984

Proc. Natl. Acad. Sci. U.S.A.

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Mammalian cardiac atria possess several unidentified biologically active peptides. Fractionation of rat atrial extracts by gel filtration chromatography revealed two major fractions [apparent molecular weights of 20,000-30,000(peak I) and <10,000 (peak II)], both of which were potent natriuretic agents (eliciting a 25-fold increase in sodium excretion) and smooth muscle relaxants. Vigorous treatment with trypsin (100 units/ml at 370C for 15 min) of both fractions abolished all biological activity. Further purification of the lower molecular weight fraction (peak II) by ion-exchange chromatography indicated two subfractions that possessed potent natriuretic activity and that preferentially relaxed either intestinal (designated peak IIA) or vascular (peak IIB) smooth muscle assay tissues. The similarity of the biological effect of the high (peak I) and low (peak II) molecular weight peptides led us to test the possibility of precursor-product relationship.Mild proteolytic treatment of the high molecular weight peptide with trypsin (1 unit/ml at room temperature) markedly enhanced the smooth muscle relaxant activity. Subsequent analysis of the trypsin (1 unit/ml)-treated high molecular weight peptide (peak I) by gel filtration and ion-exchange chromatography revealed that the peptide now resembled the low molecular weight peptides (peaks IIA and IIB) present in the original atrial extract. These data suggest that the cardiac atria contain a relatively inactive (smooth muscle relaxant) high molecular weight peptide and suggest that biologically active low molecular weight peptides can subsequently be generated by proteolytic cleavage.Recent evidence indicates that granules typical of protein secretory cells are localized in mammalian atria. The granules may be the source of an endocrine substance(s) that possibly regulates fluid balance (1, 2). The contents and function of granules located in mammalian cardiac atria remain to be established. A possible homeostatic function is implied by the demonstration that atrial stretch or myocardial volume overload cause a natriuresis and diuresis (3) and that atrial (but not ventricular) extracts possess natriuretic and diuretic activity when administered to rats (4-6). Partial purification of the atrial extract indicates the presence of several fractions with natriuretic activity (5, 6). We discovered that the crude rat atrial, but not the ventricular, extract possesses potent smooth muscle relaxant activity on isolated vascular and intestinal muscle strips (7). Because the atria are the site of fluid volume receptors, they would appear to be the ideal site for the storage and release of bioactive peptides that could participate in the fluid balance by influencing vascular tone and renal function. We separated rat atrial extracts by gel filtration into low molecular weight (<10,000) and high molecular weight (20,000-30,000) fractions, both of which were potent natriuretics when administered intravenously to rats and both of which were spasmolytic on isolated smooth mu...

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Partial Chemical Characterization of a Natriuretic Substance in Rat Atrial Heart Tissue

Cited by 69 publications

References 4 publications

Effect of atrial peptides on aldosterone production.

Effect of atrial peptides on aldosterone production.

Amino acid sequence of homologous rat atrial peptides: natriuretic activity of native and synthetic forms.

Proteolytic activation of a bioactive cardiac peptide by in vitro trypsin cleavage.

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