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Expression of Urocortin III/Stresscopin in Human Heart and Kidney

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 peptide of the corticotropin-releasing factor (CRF) family and is a specific ligand for the CRF type 2 receptor. We wished to clarify whether 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 were obtained at autopsy. These levels were comparable to the levels in pituitary (2.72 ± 0.13 pmol/g wet weight; n = 3) and brain tissues (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.

This work was supported in part by Grants-in-Aid for Scientific Research (B) (no. 13470030) and (C) (no. 13671094), and a Grant-in-Aid for Scientific Research on Priority Areas (A) (no. 13035005) from the Ministry of Education, Science, Sports, and Culture of Japan, by a research grant from the HIROMI Medical Research Foundation (2001), and by a Research Grant from the Intelligent Cosmos (2002).

Abbreviations: CRF, Corticotropin-releasing factor; IR-Ucn, immunoreactive Ucn; SCP, stresscopin; TFA, trifluoroacetic acid; Ucn, urocortin.

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