Expression of urocortin and corticotropin-releasing factor receptor subtypes in the human heart

Yuichiro Kimura, Kazuhiro Takahashi, Kazuhito Totsune, Yasunari Muramatsu, Chika Kaneko, Andrew D. Darnel, Takashi Suzuki, Masahito Ebina, Toshihiro Nukiwa, Hironobu Sasano

研究成果: Article査読

143 被引用数 (Scopus)

抄録

Urocortin (Ucn) is a new member of the corticotropin-releasing factor (CRF) neuropeptide family and has positive inotropic actions and protective effects against ischemia in the rat heart. Ucn binds with very high affinity to both CRF receptor type 1 (CRF-R1) and CRF receptor type 2 (CRF-R2). However, to date, endogenous ligand(s) for CRF receptors expressed in the human heart have yet to be elucidated. In this study, we therefore examined the expression of Ucn and CRF receptors in human heart obtained at autopsy by RT-PCR, immunohistochemistry, and RIA. RT-PCR analysis demonstrated that Ucn and CRF-R2α mRNAs were detected in all four chambers. CRF-R1 mRNA was weakly present in some left atria, left ventricles, and in one right ventricle. CRF-R2β mRNA was detected predominantly in the left atrium. CRF mRNA was not detected in any of the four chambers. Immunostaining for both Ucn and CRF receptors was detected in cardiac myocytes in all four chambers. Ucn-like immunoreactivity was detected in all four chambers by RIA, with the highest concentrations in the left ventricle (1.90 ± 0.5 pmol/g wet weight, mean ± SEM; n = 4). On the other hand, CRF-like immunoreactivity was very low or undetectable in the human heart. Sephadex G-50 column chromatography demonstrated that most of the Ucn-like immunoreactivity in the human heart was eluting earlier than the standard Ucn, with one minor peak in the position for Ucn. Ucn immunoreactivity was not detected in skeletal muscle by immunohistochemistry or RIA. These results suggest that Ucn is produced in the human heart and stored there mainly in the larger molecular weight forms. Endogenously produced Ucn may therefore exert its effects mostly through CRF-R2 in an autocrine and/or paracrine manner in the human heart.

本文言語English
ページ(範囲)340-346
ページ数7
ジャーナルJournal of Clinical Endocrinology and Metabolism
87
1
DOI
出版ステータスPublished - 2002

ASJC Scopus subject areas

  • 内分泌学、糖尿病および代謝内科学
  • 生化学
  • 内分泌学
  • 臨床生化学
  • 生化学、医学

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