1994 Fiscal Year Final Research Report Summary
Development of a CNP related drug as a new treatment for hypertension and arteriosclerosis.
| Project/Area Number |
05557051
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| Research Category |
Grant-in-Aid for Developmental Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
内分泌・代謝学
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| Research Institution | KYOTO UNIVERSITY |
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Principal Investigator |
NAKAO Kazuwa Second Division, Department of Medicine, Kyoto University Faculty of Medicine, Professor, 医学部, 教授 (00172263)
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| Co-Investigator(Kenkyū-buntansha) |
TANAKA Shoji Laboratory of Molecular Pharmacology Suntory Institute for Biomedical Research,, 生物医学研究所, 主任研究員
KANGAWA Kenji Department of Biochemistry, Director, 生化学部, 部長 (00112417)
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| Project Period (FY) |
1993 – 1994
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| Keywords | GC-B receptor / Mouse CNP gene / Cyclic GMP / cGMP |
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| Research Abstract |
CNP,the third member of the natriuretic peptide family, has been considered to act as a neuropeptide. We observed presence of three natriuretic peptides in human cerebrospinal fluid and that CNP was the major natriuretic peptide. We discovered that CNP was present mainly as CNP-53 in peripheral tissues and that CNP mRNA was present in ileum-jejum, testis, thymus, adrenal gland and submaxillary gland. We also discovered that CNP is produced and gecreted by the endothelial cells. The endothelinl secretion of CNP was regulated by interleukin Ialpha, Ibeta, transforming growth factor beta, tumor necrosis factor-alpha and also by lipopolysaccharide. Furthermore, CNP was detected in plasma of septic shock patients. The treatment of vascular smooth muscle cells with ANP,BNP of CNP decreased the C-receptor density and the rank order of potency for this downregulation was CNP>ANP>BNP.The rank order was the same as that for cGMP production and 8-bromo-cGMP significartly decreased the C-receptor density and its mRNA expression in vascular smooth muscle cells. These results suggest that the downregulation of the C-receptor is induced by the activation of the GC-B receptor/cGMP pathway. We also found that the beta2-adrenergic receptor stimulation downregulates the C-receptor through the decrease in the transcriptional rate of the C-receptor gene. The mouse CNP gene is composed of at least two exons and one intron. Mouse prepro CNP comprises 126 amimo acids and its C-terminal 22-residue peptide is identical to human CNP.The 5'-flanking region of the mouse CNP gene contains a characteristic array of cis-acting regulatory elements and a dinucleotide CA repeat.
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Research Products
(14 results)
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[Publications] Kishimoto, I., Nakao, K., Suga, S., Hosoda, K., Yoshimasa, T., Itoh, H., Imura, H.: "Down-regulation of C-receptor by natriuretic peptides via ANP-B receptor in vascular smooth muscle cells." Am.J.Physiol. 265. H1373-H1379 (1993)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Suga, S., Itoh, H., Komatsu, Y., Ogawa, Y., Hama, N., Yoshimasa, T., Nakao, K.: "Cytokine-induced C-type natriuretic peptide (CNP) secretion fromvascular endothelial cells-evidence for CNP as a novel autocrine/paracrine regulator from endothelial cell-." Endocrinology. 133. 3038-3041 (1993)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Minamino, N., Aburaya, M., Kojima, M., Miyamoto, K., Kangawa, K., Matuso.H.: "Distribution of C-type natriuretic peptide and its messengcr RNA in rat central nervous system and peripheral tisse." Biochem.Biophys.Res.Commun. 197. 326-335 (1993)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Hama, N., Itoh, H., Shirakami, G., Suga, S., Komatsu, Y., Yoshimasa, T., Tanaka, I., Mori, K., Nakao, K.: "Detection of C-type natriuretic peptide (CNP) in human circulation and marked increase of plasma CNP level in septic shock patients." Biochem.Biophys.Res.Commun. 198. 1177-1182 (1994)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Ogawa, Y., Itoh, H., Yoshitake, Y., Inoue, M., Yoshimasa, T., Serikawa, T., Nakao, K.: "Molecular cloning and chromosomal assignment of the mouse C-type natriuretic peptide (CNP) gene(Nppc) : Comparson with the human CNP gene (NPPC)." Genomics. 24. 383-387 (1994)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Kishimoto, I., Yoshimasa, T., Suga, S., Ogawa, Y., Komatsu, Y., Nakagawa, O., Itoh, H., Nakao, K.: "Natriuretic peptide clearance receptor is transcriptionally down-regulated by beta2-adrenergic stimulation in vascuar smooth musule cells." J.Biol.Chem. 269. 28300-28308 (1994)
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「研究成果報告書概要(欧文)」より
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