Departments of Molecular Biology and Applied Physiology (K.Ta., S.S.), Medicine (O.M.), and Pathology (M.S., M.N., T.S., H.S.), Tohoku University School of Medicine, Aoba-ku, Sendai, Miyagi 980-8575, Japan; and Department of Clinical Pharmacology and Therapeutics (K.To.), Tohoku University Graduate School of Pharmaceutical Science and Medicine, Aoba-ku, Sendai, Miyagi 980-8578, Japan
Address all correspondence and requests for reprints to: Kazuhiro Takahashi, M.D., Department of Molecular Biology and Applied Physiology, Tohoku University School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8575, Japan. E-mail: ktaka-md{at}mail.tains.tohoku.ac.jp.
Urocortin III (Ucn III)/stresscopin (SCP) is a novel peptideof the corticotropin-releasing factor (CRF) family and is aspecific ligand for the CRF type 2 receptor. We wished to clarifywhether Ucn III/SCP is expressed in the human heart and kidney.Immunoreactive Ucn III was detected by RIA in the human heart(0.74–1.15 pmol/g wet weight, mean ± SEM; n = 4)and kidney (1.21 ± 0.30 pmol/g wet weight), which wereobtained at autopsy. These levels were comparable to the levelsin pituitary (2.72 ± 0.13 pmol/g wet weight; n = 3) andbrain tissues (1–2 pmol/g wet weight). Furthermore, immunoreactiveUcn III was present in human plasma (51.8 ± 16.0 pmol/liter;n = 5) and urine (266 ± 20 pmol/liter; n = 5) obtainedfrom healthy subjects. Reverse-phase HPLC showed a broad peakof immunoreactive Ucn III eluting in the position of syntheticUcn III in the heart, kidney, and hypothalamus. Material elutingin the position of SCP was also found in the HPLC analysis ofthese tissue extracts. Immunocytochemistry showed positive stainingof Ucn III in the myocardium and the renal tubules, particularlydistal tubules. RT-PCR showed expression of Ucn III mRNA inthe brain, pituitary, heart, and kidney. The present study hasshown expression of Ucn III/SCP in the human heart and kidneyas well as brain and pituitary tissues and its presence in plasmaand urine. Ucn III/SCP may therefore regulate the cardiac andrenal function as a local factor and a circulating hormone.
This work was supported in part by Grants-in-Aid for ScientificResearch (B) (no. 13470030) and (C) (no. 13671094), and a Grant-in-Aidfor Scientific Research on Priority Areas (A) (no. 13035005)from the Ministry of Education, Science, Sports, and Cultureof Japan, by a research grant from the HIROMI Medical ResearchFoundation (2001), and by a Research Grant from the IntelligentCosmos (2002).
A. Yata, K. Nakabayashi, S. Wakahashi, N. Maruo, N. Ohara, and T. Maruo Suppression of progesterone production by stresscopin/urocortin 3 in cultured human granulosa-lutein cells
Hum. Reprod.,
July 1, 2009;
24(7):
1748 - 1753.
[Abstract][Full Text][PDF]
K. Ikeda, K. Tojo, Y. Inada, Y. Takada, M. Sakamoto, M. Lam, W. C Claycomb, and N. Tajima Regulation of urocortin I and its related peptide urocortin II by inflammatory and oxidative stresses in HL-1 cardiomyocytes
J. Mol. Endocrinol.,
June 1, 2009;
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479 - 489.
[Abstract][Full Text][PDF]
T. Nakamura, K. Kawabe, and H. N. Sapru Cardiovascular responses to microinjections of urocortin 3 into the nucleus tractus solitarius of the rat
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February 1, 2009;
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H325 - H332.
[Abstract][Full Text][PDF]
M. T. Rademaker, V. A. Cameron, C. J. Charles, and A. M. Richards Urocortin 3: haemodynamic, hormonal, and renal effects in experimental heart failure
Eur. Heart J.,
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2088 - 2098.
[Abstract][Full Text][PDF]
E. W. Hillhouse and D. K. Grammatopoulos The Molecular Mechanisms Underlying the Regulation of the Biological Activity of Corticotropin-Releasing Hormone Receptors: Implications for Physiology and Pathophysiology
Endocr. Rev.,
May 1, 2006;
27(3):
260 - 286.
[Abstract][Full Text][PDF]
K. Takahashi, M. T. Rademaker, V. A. Cameron, C. J. Charles, and A. M. Richards Letter Regarding Article by Rademaker et al, "Integrated Hemodynamic, Hormonal, and Renal Actions of Urocortin 2 in Normal and Paced Sheep: Beneficial Effects in Heart Failure"
Circulation,
April 18, 2006;
113(15):
e710 - e710.
[Full Text][PDF]
M. T. Rademaker, C. J. Charles, E. A. Espiner, C. M. Frampton, J. G. Lainchbury, and A. M. Richards Endogenous urocortins reduce vascular tone and renin-aldosterone/endothelin activity in experimental heart failure
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[Abstract][Full Text][PDF]
T. Fukuda, K. Takahashi, T. Suzuki, M. Saruta, M. Watanabe, T. Nakata, and H. Sasano Urocortin 1, Urocortin 3/Stresscopin, and Corticotropin-Releasing Factor Receptors in Human Adrenal and Its Disorders
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August 1, 2005;
90(8):
4671 - 4678.
[Abstract][Full Text][PDF]
1–2 pmol/g wet weight). Furthermore, immunoreactive Ucn III was present in human plasma (51.8 ± 16.0 pmol/liter; n = 5) and urine (266 ± 20 pmol/liter; n = 5) obtained from healthy subjects. Reverse-phase HPLC showed a broad peak of immunoreactive Ucn III eluting in the position of synthetic Ucn III in the heart, kidney, and hypothalamus. Material eluting in the position of SCP was also found in the HPLC analysis of these tissue extracts. Immunocytochemistry showed positive staining of Ucn III in the myocardium and the renal tubules, particularly distal tubules. RT-PCR showed expression of Ucn III mRNA in the brain, pituitary, heart, and kidney. The present study has shown expression of Ucn III/SCP in the human heart and kidney as well as brain and pituitary tissues and its presence in plasma and urine. Ucn III/SCP may therefore regulate the cardiac and renal function as a local factor and a circulating hormone. 
