Urocortin, a member of the corticotropin-releasing factor family, in normal and diseased heart.
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.
Nishikimi
T
T
Research Institute, National Cardiovascular Center, Suita, Osaka 565, Japan. nishikim@dokkyomed.ac.jp
Miyata
A
A
Horio
T
T
Yoshihara
F
F
Nagaya
N
N
Takishita
S
S
Yutani
C
C
Matsuo
H
H
Matsuoka
H
H
Kangawa
K
K
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000378:metabolism; D002250:Carbon Radioisotopes; D002478:Cells, Cultured; D003346:Corticotropin-Releasing Hormone / Q000032:analysis / Q000235:genetics* / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D015870:Gene Expression / Q000502:physiology; D006333:Heart Failure / Q000473:pathology*; D006727:Hormone Antagonists / Q000494:pharmacology; D017379:Hypertrophy, Left Ventricular / Q000473:pathology*; D007150:Immunohistochemistry; D018485:Muscle Fibers, Skeletal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009206:Myocardium / Q000737:chemistry / Q000166:cytology*; D010446:Peptide Fragments / Q000494:pharmacology; D010649:Phenylalanine / Q000493:pharmacokinetics; D011392:Proline / Q000493:pharmacokinetics; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D018019:Receptors, Corticotropin-Releasing Hormone / Q000235:genetics; D013936:Thymidine / Q000493:pharmacokinetics; D014316:Tritium; D054832:Urocortins; D000099052:CRF Receptor, Type 1
C101531:CRF receptor type 2; C101518:CRF(2alpha) receptor; D002250:Carbon Radioisotopes; D006727:Hormone Antagonists; D010446:Peptide Fragments; D012333:RNA, Messenger; D018019:Receptors, Corticotropin-Releasing Hormone; D054832:Urocortins; D014316:Tritium; D010649:Phenylalanine; D000099052:CRF Receptor, Type 1; D009320:Atrial Natriuretic Factor; D003346:Corticotropin-Releasing Hormone; C045089:corticotropin releasing hormone (9-41); D011392:Proline; D000242:Cyclic AMP; D013936:Thymidine