C-Type Natriuretic Peptide (Cnp) in Rats and Humans

Komatsu, Yasato; Nakao, Kazuwa; Suga, Shin Ichi; Ogawa, Yoshihiro; Mukoyama, Masashi; Arai, Hiroshi; Shirakami, Gotaro; Hosoda, Kiminori; Nakagawa, Osamu; Hama, Norio; Kishimoto, Ichiro; Imura, Hiroo

doi:10.1210/endo-129-2-1104

Cited by 280 publications

(122 citation statements)

References 16 publications

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“…As for the subtype of the biologically active receptors, the ANP-A receptor is predominantly expressed in PC12 cells, bovine EC, and LLC-PK, cells, whereas the ANP-B receptor is predominant in rat aortic SMC and human mesangial cells. Since CNP is distributed mainly in the brain, 9 the significance of the abundant expression of the ANP-B receptor in mesangial cells and aortic SMC remains to be resolved. However, we have reported that CNP exists in peripheral organs, such as in pituitary, kidney, and colon.…”

Section: Discussionmentioning

confidence: 99%

“…However, we have reported that CNP exists in peripheral organs, such as in pituitary, kidney, and colon. 9 Therefore, CNP may act as a local regulator through interaction with the ANP-B receptor.…”

Section: Discussionmentioning

confidence: 99%

“…1 " 9 Receptors for natriuretic peptides have been shown to exist in various target tissues and cells. 510 " 13 Two distinct types of receptors have been identified.…”

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Characterization of natriuretic peptide receptors in cultured cells.

et al. 1992

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To elucidate physiological and clinical implications of the natriuretic peptide family, the expression of receptors for natriuretic peptides has been examined in cultured cells (a rat pheochromocytoma cell line [PC12], bovine endothelial cells, rat aortic smooth muscle cells, human mesangial cells, and a porcine kidney epithelial cell line [LLC-PK,]) by Northern blot analysis and cyclic GMP production method for the ANP-A and ANP-B receptors and by Northern blot analysis and binding assay for the clearance receptor. The ANP-A receptor was predominantly expressed in PC12 cells, bovine endothelial cells, and LLC-PK, cells but was barely expressed in rat aortic smooth muscle cells and human mesangial cells. By contrast, the ANP-B receptor was the major subtype of the biologically active receptors in rat aortic smooth muscle cells and human mesangial cells. Only a small amount of the ANP-B receptor was detected in PC12 cells, bovine endothelial cells, and LLC-PK, cells. The clearance receptor was abundantly expressed in rat aortic smooth muscle cells and human mesangial cells and was also present in bovine endothelial cells, but it was undetectable in PC12 cells and LLC-PK, cells. These results demonstrate that the expression of three natriuretic peptide receptors varies from cell to cell, which is relevant to cell-or tissue-specific action of the natriuretic peptide family. 14 and is designated as the biologically active receptor. Molecular cloning has revealed the existence of two subtypes of biologically active receptors, the ANP-A receptor and ANP-B receptor. 15The other type of receptor is not coupled to guanylate cyclase 16 and is proposed to have a major role in the clearance of natriuretic peptides. 10 This receptor is, therefore, termed the clearance receptor (C receptor).Recently, we and others have demonstrated that ANP is a selective ligand for the ANP-A receptor, with the rank order of potency for cyclic GMP (cGMP) production ANP>BNP>>CNP, and that CNP is selective for the ANP-B receptor, with the rank order of potency CNP>ANP>BNP. 1217 We have also revealed the C receptor selectivity with the rank order of the binding affinity, ANP>CNP>BNP.12 Knowledge of the expression of three receptors for natriuretic peptides at the cellular level have, therefore, important functional consequence.From the Second Division, Department of Medicine, Kyoto University School of Medicine, Kyoto, Japan.Address for correspondence: Kazuwa Nakao, MD, PhD, Second Division, Department of Medicine, Kyoto University School of Medicine, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606, Japan.In the present study, to elucidate the physiological and clinical implications of the natriuretic peptide family, the expression of the three kinds of natriuretic peptide receptors was examined in various cultured cells with the binding assay, cGMP production method, and Northern blot analysis. Methods Cell CultureA rat pheochromocytoma cell line (PC12), rat aortic smooth muscle cells (SMC), bovine endothelial cells (EC), and human mesangial cel...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Characterization of natriuretic peptide receptors in cultured cells.

et al. 1992

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“…ANPB receptors have been detected in brain microvessel endothelial cells, but not in aortic endothelial cells, which express ANPA receptors (Vigne & Frelin, 1992). The possible role of CNP (apparently a brain-restricted peptide, Kojima et al, 1990;Komatsu et al, 1991) in the cerebellum and whether CNP interacts with the cerebral microvasculature require further investigation. Although there is evidence for ANP and/or the C-receptor coupling to phosphoinositide turnover in other systems (see Introduction), we were unable to observe an increase in…”

Section: Effects Of Natriuretic Peptides On Cyclic Amp Generationmentioning

confidence: 96%

Natriuretic peptide‐induced cyclic GMP accumulation in adult guinea‐pig cerebellar slices

Hernández

Alexander

Kendall

1994

British J Pharmacology

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“…CNP, the third member of natriuretic peptide family, was first purified from porcine brain [18]. While CNP is the primary natriuretic peptide in the human brain [19], it is also produced by vascular endothelial cells [20][21][22] and macrophages [23], and is thought to act as an autocrine/paracrine regulator and as a neuropeptide [19]. Furthermore, analysis of genetically engineered mice of the CNP/GC-B system revealed that CNP and GC-B play a pivotal role in the regulation of endochondral bone growth.…”

Section: Abstract: C-type Natriuretic Peptide (Cnp) Guanylyl Cyclasmentioning

confidence: 99%

Translational research of C-type natriuretic peptide (CNP) into skeletal dysplasias

Yasoda

Nakao

2010

Endocr J

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Abstract. By using transgenic and knockout mice, we have elucidated that C-type natriuretic peptide (CNP) is a potent stimulator of endochondral bone growth. In humans, loss-of-function mutations in the gene coding for guanylyl cyclase-B (GC-B), the specific receptor for CNP, have been proved to be the cause of acromesomelic dysplasia, type Maroteaux, one form of human skeletal dysplasias. Following these results, we have started to translate the stimulatory effect of CNP on endochondral bone growth into the therapy for patients with skeletal dysplasias. We have shown that targeted overexpression of CNP in cartilage or systemic administration of CNP reverses the impaired skeletal growth of mice model of achondroplasia, the most common form of human skeletal dysplasias. Key words: C-type natriuretic peptide (CNP), Guanylyl cyclase-B (GC-B), Skeletal dysplasia, Achondroplasia, Translational researchThe nATriureTic peptide family consists of three structurally related peptides, atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP) [1]. The biological actions of natriuretic peptides are mediated by activation of two subtypes of membranous guanylyl cyclase (GC), GC-A and GC-B, followed by intracellular accumulation of cyclic GMP (cGMP) [2]. The rank order of potency to induce cGMP production via GC-A is ANP ≥ BNP >> CNP, while that via GC-B is CNP > ANP ≥ BNP [3]. Therefore, ANP and BNP serve as endogenous ligands for GC-A, whereas CNP is specific for GC-B. A third natriuretic peptide receptor with no intracellular guanylyl cyclase domain, dubbed the clearance receptor (C-receptor), is thought to be engaged in the receptor-mediated degradation of natriuretic peptides [2]. The ANP, BNP/GC-A system plays a pivotal role in the regulation of cardiovascular homeostasis, as demonstrated by their augmentation in various pathophysiological states such as heart failure [4][5][6][7][8], myocardial infarction [9, 10], cardiac hypertrophy [11,12], and hypertension [13][14][15]. In fact, ANP and BNP are cardiac hormones secreted primarily by the atrium and ventricle of the heart, respectively [8,15], with strong diuretic, natriuretic, and vasodilatory activities [4, 5, 8]. ANP and BNP are used in the treatment of heart failure [16,17] and serve as sensitive biochemical markers for heart failure and cardiac hypertrophy [6][7][8]. CNP, the third member of natriuretic peptide family, was first purified from porcine brain [18]. While CNP is the primary natriuretic peptide in the human brain [19], it is also produced by vascular endothelial cells [20][21][22] and macrophages [23], and is thought to act as an autocrine/paracrine regulator and as a neuropeptide [19]. Furthermore, analysis of genetically engineered mice of the CNP/GC-B system revealed that CNP and GC-B play a pivotal role in the regulation of endochondral bone growth.i. The growth promoting effect of the cnP/Gc-B system on endochondral bone growth I-1. Skeletal phenotypes of genetically engineered mice of the CNP/GC-B sys...

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C-Type Natriuretic Peptide (Cnp) in Rats and Humans

Cited by 280 publications

References 16 publications

Characterization of natriuretic peptide receptors in cultured cells.

Characterization of natriuretic peptide receptors in cultured cells.

Natriuretic peptide‐induced cyclic GMP accumulation in adult guinea‐pig cerebellar slices

Translational research of C-type natriuretic peptide (CNP) into skeletal dysplasias

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