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PMID:11087261

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Citation

Nishikimi, T, Miyata, A, Horio, T, Yoshihara, F, Nagaya, N, Takishita, S, Yutani, C, Matsuo, H, Matsuoka, H and Kangawa, K (2000) Urocortin, a member of the corticotropin-releasing factor family, in normal and diseased heart. Am. J. Physiol. Heart Circ. Physiol. 279:H3031-9

Abstract

In the present study we investigated the form of expression, action, second messenger, and the cellular location of urocortin, a member of the corticotropin-releasing factor (CRF) family, in the heart. Urocortin mRNA, as shown by quantitative RT-PCR analysis, is expressed in the cultured rat cardiac nonmyocytes (NMC) as well as myocytes (MC) in the heart, whereas CRF receptor type 2beta (CRF-R2beta), presumed urocortin receptor mRNA, is predominantly expressed in MC compared with NMC. Urocortin mRNA expression is higher in left ventricular (LV) hypertrophy than in normal LV, whereas CRF-R2beta mRNA expression is markedly depressed in LV hypertrophy compared with normal LV. Urocortin more potently increased the cAMP levels in both MC and NMC than did CRF, and its effect was more potent in MC than in NMC. Urocortin significantly increased protein synthesis by [(14)C]Phe incorporations and atrial natriuretic peptide secretion in MC and collagen and increased DNA synthesis by [(3)H]prolin and [(3)H]Thy incorporations in NMC. An immunohistochemical study revealed that urocortin immunoreactivity was observed in MC in the normal human heart and that it was more intense in the MC of the human failing heart than in MC of the normal heart. These results, together with the recent evidence of urocortin for positive inotropic action, suggest that increased urocortin in the diseased heart may modulate the pathophysiology of cardiac hypertrophy or failing heart, at least in part, via cAMP signaling pathway.

Links

PubMed

Keywords

Animals; Atrial Natriuretic Factor/metabolism; Carbon Radioisotopes/diagnostic use; Cells, Cultured; Corticotropin-Releasing Hormone/analysis; Corticotropin-Releasing Hormone/genetics; Corticotropin-Releasing Hormone/pharmacology; Cyclic AMP/metabolism; Gene Expression/physiology; Heart Failure/pathology; Hormone Antagonists/pharmacology; Hypertrophy, Left Ventricular/pathology; Immunohistochemistry; Muscle Fibers, Skeletal/cytology; Muscle Fibers, Skeletal/drug effects; Muscle Fibers, Skeletal/metabolism; Myocardium/chemistry; Myocardium/cytology; Peptide Fragments/pharmacology; Phenylalanine/pharmacokinetics; Proline/pharmacokinetics; RNA, Messenger/analysis; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Receptors, Corticotropin-Releasing Hormone/genetics; Thymidine/pharmacokinetics; Tritium/diagnostic use; Urocortins

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

RAT:UCN1

involved_in

GO:0045740: positive regulation of DNA replication

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

RAT:UCN1

involved_in

GO:0045727: positive regulation of translation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

RAT:UCN1

involved_in

GO:0032967: positive regulation of collagen biosynthetic process

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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