Purification and subunit composition of atrial natriuretic peptide receptor.

Schenk, Dale; Phelps, M.; Porter, J G; Fuller, Forrest; Cordell, Barbara; Lewicki, John

doi:10.1073/pnas.84.6.1521

Cited by 95 publications

(29 citation statements)

References 31 publications

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“…However, the cloned gene from rat intestinal cells had again predicted a high-M, species as the ST receptor 1311, and it is possible that the low-M, forms may be detected preferentially using the cross-linkers employed in the earlier studies. Alternatively, they may be proteolytically degraded fragments of the native high-Mr rat receptor, or truncated forms of the receptor, as have been described for the atrial natriuretic factor receptor [36,371, which may be involved in a regulation of the ST-mediated response in intestinal cells.…”

Section: Affinity Cross-linking Of St Y72f To the Solubilised Receptormentioning

confidence: 99%

Characterization and partial purification of the human receptor for the heat‐stable enterotoxin

Visweswariah¹,

Ramachandran²,

Ramamohan³

et al. 1994

European Journal of Biochemistry

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The receptor for the Escherichia coli heat-stable enterotoxin has been characterized and partially purified from the T84 human colonic cell line. Using a novel mutant heat-stable enterotoxin peptide as a radioligand (the C-terminal tyrosine residue is replaced by phenylalanine in the mutant), a single class of high-affinity receptor sites was detected in T84 cells, with a Kd of 0.1 nM, similar in affinity to the receptor described in human intestinal tissue. The receptor was solubilised from T84 cell membranes and affinity cross-linking of the solubilised preparation indicated that a single species of M, 160000 served as the receptor. Freshly solubilised preparations of the receptor retained heat-stable enterotoxin-activable guanylyl cyclase activity. Purification of the receptor was achieved through sequential affinity chromatography on GTP-epoxy-Sepharose and wheat-germ-agglutinin columns resulting in purification of the receptor by 3000 fold. The heat-stable enterotoxin-binding characteristics of the receptor were unchanged during the purification and silver staining of the purified receptor preparation indicated a band of M, 160000, which was specifically cross-linked to the lZ51-labeled mutant peptide. The purified receptor retained guanylyl cyclase activity, but the activity was not stimulated on addition of human heat-stable enterotoxin, suggesting that accessory structural factors may be involved in the activation of the guanylyl cyclase/receptor.The heat-stable enterotoxins (ST) are a family of lowmolecular-mass peptide toxins, and are one of the major causes of watery secretory diarrhoea all over the world [1, 21. Various forms of the toxins, differing in amino acid sequence, are produced by a number of pathogenic bacteria [3, 41, and all these peptides contain a cysteine-rich core essential for full biological activity [5, 61. ST peptides bind to a receptor on intestinal cells and activate membrane-bound guanylyl cyclase [7, 81. Increased levels of cyclic GMP (cGMP) within the cell are hypothesised to lead to enhanced C1-secretion from the intestinal cell by as yet undefined mechanisms, resulting in fluid loss and subsequent diarrhoea Early biochemical studies had postulated that in rat intestinal membranes the ST-binding and guanylyl cyclase activities were located on separate molecules [lo]. However, the cloning and expression of the rat and human intestinal ST receptor [ll-131 suggested that the ST receptor was in fact a high-molecular-mass protein and a member of the guanylyl cyclase family of receptors, described earlier for atrial natriuretic factor and the sea urchin egg peptides [14]. These observations implied that the ST-binding and guanylyl cyclase activities were present in the same receptor molecule. How- ever, there is no biochemical evidence using purified receptor preparations to confirm that the ST receptor does in fact exist in the cell as suggested for the recombinant protein. Hugues et al. reported the purification of the rat ST receptor from intestinal membranes using ST-ligand af...

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Section: Affinity Cross-linking Of St Y72f To the Solubilised Receptormentioning

confidence: 99%

Characterization and partial purification of the human receptor for the heat‐stable enterotoxin

Visweswariah¹,

Ramachandran²,

Ramamohan³

et al. 1994

European Journal of Biochemistry

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“…It has frequently been assumed that the low-molecularmass receptors found in various organs represent an ANF clearance receptor (C-receptor; Maack et al, 1987), which has been described by Scarborough et al (1986) and Schenk et al (1987), and later cloned from cultured vascular smooth muscle cells (Fuller et al, 1988). The C-receptor sequence contains an extracellular ANF-binding domain, a transmembrane sequence and a short intracellular tail.…”

mentioning

confidence: 99%

Proteolytic cleavage of atrial natriuretic factor receptor in bovine adrenal membranes by endogenous metalloendopeptidase

Abe

Misono

1992

European Journal of Biochemistry

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Atrial natriuretic factor (ANF) is a peptide hormone from the heart atrium with potent natriuretic and vasorelaxant activities. The natriuretic activity of ANF is, in part, mediated through the adrenal gland, where binding of ANF to the 130-kDa ANF receptor causes suppression of aldosterone secretion. Incubation of bovine adrenal membranes at pH (5.6 caused a rapid and spontaneous cleavage of the 130-kDa ANF receptor, yielding a 65-kDa polypeptide that could be detected by photoaffinity labeling by 1251-labeled W4-azidobenzoyl-ANF(4 -28) followed by SDSjPAGE under reducing conditions. Within 20 min of incubation at pH 4.0, essentially all the 130-kDa receptor was converted to a 65-kDa ANF binding protein. This cleavage reaction was completely inhibited by inclusion of 5 mM EDTA. When SDSjPAGE was carried out under non-reducing conditions, the apparent size of the ANF receptor remained unchanged at 130 kDa, indicating that the 65-kDa ANFbinding fragment was still linked to the remaining part(s) of the receptor polypeptide through a disulfide bond(s). The disappearance of the 130-kDa receptor was accompanied by a parallel decrease in guanylate cyclase activity in the membranes. Inclusion of EDTA in the incubation not only prevented cleavage of the 130-kDa receptor, but also protected guanylate cyclase activity, indicating that proteolysis, but not the physical effects of the acidic pH, causes inactivation of guanylate cyclase. The 130-kDa ANF receptor in adrenal membranes was competitively protected from photoaffinity labeling by ANF(1-28) or ANF(4 -28), but not by atriopeptin I [ANF(5 -25)] or C-ANF [des-(18 -22)-ANF(4-23)-NH2]. On the contrary, the 65-kDa ANF-binding fragment generated after incubation at pH 4.0 was protected from labeling by any of the above peptides, indicating broader binding specificity. After incubation in the presence of EDTA, the 130-kDa ANF receptor, which was protected from proteolysis, retained binding specificity identical to that of the 130-kDa receptor in untreated membranes. The results indicate that the broadening of selectivity is caused by cleavage, but not by the physical effect of acidic pH. Spontaneous proteolysis of ANF receptor by an endogenous metalloendopeptidase, occurring with concomitant inactivation of guanylate cyclase activity and broadening of ligand-binding selectivity, may be responsible for the generation of low-molecularmass receptors found in the adrenal gland and other target organs of ANF. The proteolytic process may play a role in desensitization or down-regulation of the ANF receptor.

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“…9 Activation of NPRC results in the inhibition of adenylyl cyclase activity. 10 Human NPRA (hNPRA) has high structural homology with human NPRB (hNPRB) and also contains a highly conserved guanylyl cyclase domain. 5 ANP and BNP bind primarily to NPRA, which exerts its effect on the vasculature, causing vasodilation and inhibition of the proliferation of vascular smooth muscle cells.…”

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confidence: 99%

Functional Deletion Mutation of the 5′-Flanking Region of Type A Human Natriuretic Peptide Receptor Gene and Its Association With Essential Hypertension and Left Ventricular Hypertrophy in the Japanese

Nakayama

Soma

Takahashi

et al. 2000

Circulation Research

122

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Abstract-The natriuretic peptide (NP) family is involved in the regulation of blood pressure and fluid volume. We isolated the 5Ј-flanking region of the type A human NP receptor gene and identified an insertion/deletion mutation in this region. We then assessed whether there is a genetic association between this mutation and essential hypertension (EH). The deletion allele lacks 8 nucleotides and alters binding sites for the activator protein-2 (AP-2) and Zeste transcriptional factors. We genotyped 200 EH and 200 normotensive (NT) individuals and found 9 subjects with the deletion (8 in the EH group and 1 in the NT group). All 9 individuals were heterozygous. The NT subject with the mutation had left ventricular hypertrophy without hypertension. Transcriptional activity of the deletion allele was Ͻ30% that of the wild-type allele. The plasma levels of brain NP in EH patients with the deleted allele were significantly higher than the levels in the EH patients with the wild-type allele, and plasma brain NP levels were significantly higher in subjects with the deleted allele than in subjects with the wild-type allele, despite comparable blood pressures. These findings suggest that in Japanese individuals, this deletion in the human NP receptor gene reduces receptor activity and may confer increased susceptibility to developing EH or left ventricular hypertrophy. Key Words: natriuretic peptides Ⅲ type A receptors Ⅲ 5Ј-flanking region Ⅲ essential hypertension T hree types of natriuretic peptides (NPs) have been isolated: atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP). The NP family elicits a number of vascular, renal, and endocrine effects that help maintain blood pressure and extracellular fluid volume. 1-3 These effects are mediated by specific binding of NP to cell surface receptors that have been characterized, purified, and cloned from the vasculature, kidney, adrenal gland, and brain. 4 -7 There are 3 subtypes of NP receptors: type A NP receptor (NPRA), 4 type B NP receptor (NPRB), 8 and type C NP receptor (NPRC). 5 All 3 influence cellular second messengers. NPRA and NPRB are guanylyl cyclase receptors, and their activation increases cGMP levels. 9 Activation of NPRC results in the inhibition of adenylyl cyclase activity. 10 Human NPRA (hNPRA) has high structural homology with human NPRB (hNPRB) and also contains a highly conserved guanylyl cyclase domain. 5 ANP and BNP bind primarily to NPRA, which exerts its effect on the vasculature, causing vasodilation and inhibition of the proliferation of vascular smooth muscle cells. 11 Essential hypertension (EH) is thought to be a multifactorial disorder, and there are only a few reports of candidate genes associated with EH. 12 Mice with a targeted deletion of NPRA showed hypertension, cardiac hypertrophy, and sudden death. 13 These findings suggest that NPRA may play key roles in vasodilation, maintenance of blood pressure, and cardiac remodeling and that lack of it may lead to hypertension and other cardiov...

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Purification and subunit composition of atrial natriuretic peptide receptor.

Cited by 95 publications

References 31 publications

Characterization and partial purification of the human receptor for the heat‐stable enterotoxin

Characterization and partial purification of the human receptor for the heat‐stable enterotoxin

Proteolytic cleavage of atrial natriuretic factor receptor in bovine adrenal membranes by endogenous metalloendopeptidase

Functional Deletion Mutation of the 5′-Flanking Region of Type A Human Natriuretic Peptide Receptor Gene and Its Association With Essential Hypertension and Left Ventricular Hypertrophy in the Japanese

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