Synthesis of atrial natriuretic peptides and studies on structural factors in tissue specificity

Sugiyama, M.; Fukumi, Hiroshi; Grammer, Robert T.; Misono, Kunio S.; Yabe, Yuichiro; Morisawa, Yuji; Inagami, Tadashi

doi:10.1016/0006-291x(84)90418-2

Cited by 85 publications

(23 citation statements)

References 12 publications

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“…In the pulmonary artery the decreased potency ofthese peptides when compared to ANP was correlated with the loss of amino acids from the parent ANP molecule. The finding that AP I produced some degree of vasorelaxation is in contrast to the results of other workers Oshimi et al, 1984), but corresponds to the data of Sugiyama et al (1984). Because circulating levels of these peptides are much lower than those ofANP, they are unlikely to have a role in the physiological maintenance of pulmonary arterial tone.…”

Section: Discussionsupporting

confidence: 78%

A comparison of the vasodilator responses to atrial peptides in the pulmonary and renal arteries of the pig in vitro

Jansen¹,

Morice²

1987

British J Pharmacology

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1Noradrenaline preconstricted pulmonary. and renal artery segments from 20 large White pigs were examined in vitro for their responses to a-human atrial natriuretic peptide (a-hANP), rat-atriopeptin I (AP I) or rat-atriopeptin III (AP III) added in a cumulative manner. The role of the vascular endothelium in atrial peptide-induced relaxation was examined in the presence of indomethacin and propranolol by removal of the endothelium in one of a pair of arterial segments. 2 Pulmonary artery was significantly (P <0.001) more sensitive than renal artery to a-hANP with a potency ratio ofapproximately 10. a-hANP appeared to be a more potent relaxant than AP III and AP I in pulmonary artery. Potency ratios were approximately 2 (AP III vs a-hANP; P < 0.05) and 30 (AP I vs aE-ANP; P<0.001). 3 Removal of the endothelium increased the sensitivity of renal artery to a a-hANP, but made no difference to the pulmonary arterial relaxations. 4 In man the highest circulating concentrations of ANP are found in the pulmonary artery. The demonstration of its potent relaxant effects at this site in the pig indicates a possible role in the modulation of pulmonary arterial tone.

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Section: Discussionsupporting

confidence: 78%

A comparison of the vasodilator responses to atrial peptides in the pulmonary and renal arteries of the pig in vitro

Jansen¹,

Morice²

1987

British J Pharmacology

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“…However, as obtained in binding assays, it seems that the deletion of the COOHterminal tyrosine residue decreases the biological activity of ANP-like peptides in bioassays such as kidney (natriuretic activity) (40)(41)(42), rabbit aorta (40,42), chicken rectum (40,42), and secretion of aldosterone by the adrenal gland (42). Little is currently known on the possible relevance of ANP/ANF receptor binding sites in the central nervous system.…”

Section: Resultsmentioning

confidence: 99%

Characterization and distribution of receptors for the atrial natriuretic peptides in mammalian brain.

Quirion¹,

Dalpé²,

Dam³

1986

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

149

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Various atrial natriuretic peptides have been isolated recently from secretory-like granules present in the myocytes of mammalian atria. These include the atrial natriuretic factors (ANF) (1-8), atrial natriuretic polypeptides (ANP) (9, 10), auriculins (9), atriopeptins (11-13), cardionatrins (14-16), and cardiodilatin (5, 17). As revealed by cDNA analysis, all of these peptides are likely to be derived from a multihormone precursor (18)(19)(20)(21)(22)(23)(24)(25). Strong sequence homology between rat and human ANP demonstrates the conservation of amino acid composition during mammalian evolution (1-17). These various peptides modulate blood-pressure homeostasis, aldosterone production, and extracellular fluid volume (for review, see refs. 7 and 26) by acting as a circulating hormone stimulated by volume loading (27). Recently, the presence of ANP or ANF-like immunoreactivity (28,29) in rat brain has been demonstrated. We also provided preliminary evidence for the existence of ANF binding sites in rat brain, using an autoradiographic technique (30). However, essential saturation analysis and ligand selectivity pattern were not obtained because of the low density of sites in most regions of the rat brain.Here we report on the characterization and differential autoradiographic distribution of ANP receptor binding sites in various mammalian brains. In the guinea pig brain, 125I-labeled ANP (12-I-ANP) binds with high affinity (Kd between 0.02 and 0.08 nM) to receptor sites that are mainly concentrated in the olfactory bulb, subfornical organ, paraventricular, paratenial, paracentral, and centrolateral nuclei of the thalamus, hippocampus, medial geniculate nucleus, and lobules 9 and 10 of the cerebellum. The high density ofANP binding sites in these various regions suggests the possible existence of a family of brain-heart peptides that could act as neurotransmitters/neuromodulators, in analogy to the well-known brain-gut peptides. MATERIALS AND METHODSIn preliminary experiments, we observed that the guinea pig cerebellum and thalamus/hypothalamus area were enriched in 1251-ANP binding sites. In other regions such as the striatum, cortex, and brain stem, it was not possible to perform appropriate receptor binding studies (saturation, ligand selectivity pattern) because ofthe low densities ofsites in these areas. Thus, we used those first two brain regions to further characterize those sites. Male guinea pigs (500 g) were decapitated, and the thalamus/hypothalamus area and the cerebellum were rapidly dissected out on ice before homogenization in 10 vol of 150 mM Tris HCl buffer (pH 7.4 at 4°C) containing 120 mM NaCl and 5 mM KCl using a Brinkmann polytron at setting 6 for 20 sec. Homogenates were then centrifuged for 10 min at 49,000 x g. Supernatants were discarded, and pellets were resuspended in 50 mM Tris'HCl buffer (pH 7.4 at 4°C) containing 300 mM KCl and 10 mM Na2EDTA before incubation on ice for 30 min with gentle agitation. After centrifugation as above, pellets were resuspended in 20 vol of 50 mM Tris HCl b...

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“…The ANF of 25 amino acids synthesized by Sugiyama et al (1984) has been shown to have chemical characteristics and biological activities that match those of natural ANF which was extracted from rat atrium and sequenced by Misono et al (1984). Assuming that ANF did not degrade during the study, and that the pumps dispensed fluid at the specified rate of approximately 0.5 ,u1/hr, the infusion dose of ANF (150 ,u g/kg/day) was chosen to be sufficient to induce small but significant diuresis and natriuresis, and not to affect blood pressure in a rat bioassay system (Yasujima et al 1985).…”

Section: Methodsmentioning

confidence: 99%

Acute and chronic effects of synthetic atrial natriuretic factor on blood pressure and sodium excretion in spontaneously hypertensive rats.

Kohzuki

Abe

Yasujima

et al. 1989

Tohoku J. Exp. Med.

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To assess possible roles of atrial natriuretic factor (ANF) in the regulation of blood pressure in spontaneously hypertensive rats (SHR), we performed two series of experiments. First, we studied acute hypotensive, natriuretic and diuretic effects of ANF in pentobarbital-anesthetized SHR and age-matched Wistar-Kyoto rats (WKY). A synthetic ANF of 25 amino acid residues was intravenously administered as a bolus at doses of 0.1, 1.0, 2.5 and 5.0 p g/kg. In SHR group, a significant decrease in mean arterial pressure (MAP) was observed at a dose of 1.0 pg/kg, and the decrease was dose-dependent. On the other hand, in WKY group, the hypotensive effect of ANF was not observed until a dose of 5.0 pg/kg. The diuretic and natriuretic effects of ANF were observed at a dose of 2.5 p g/kg in SHR and 5.0 p g/kg in WKY, respectively. Second, we also studied chronic effect of ANF on the development of hypertension in 6-week-old SHR. The SHRs, on regular diet or given 1% NaCI solution for drinking, were continuously infused into the jugular vein by osmotic minipumps with ANF (15, 75 and 150pg/kg/day) or vehicle (physiological saline) as controls for up to 14 days. ANF at a dose of 150 p g/kg/day attenuated transiently the development of hypertension in the sodium-loaded SHR. However, the blood pressure returned to control levels by day 5. ANF at doses of 15 and 75pg/kg/day did not affect the development of hypertension. In SHR on regular diet, ANF at a dose of 150 p g/ kg/day did not affect the development of hypertension. In addition, ANF did not induce any significant changes in urine volume, fluid intake, and urinary excretion

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Synthesis of atrial natriuretic peptides and studies on structural factors in tissue specificity

Cited by 85 publications

References 12 publications

A comparison of the vasodilator responses to atrial peptides in the pulmonary and renal arteries of the pig in vitro

A comparison of the vasodilator responses to atrial peptides in the pulmonary and renal arteries of the pig in vitro

Characterization and distribution of receptors for the atrial natriuretic peptides in mammalian brain.

Acute and chronic effects of synthetic atrial natriuretic factor on blood pressure and sodium excretion in spontaneously hypertensive rats.

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