Molecular cloning of human prostacyclin receptor cDNA and its gene expression in the cardiovascular system

Osamu Nakagawa, Issei Tanaka, Takeshi Usui, Masaki Harada, Yutaka Sasaki, Hiroshi Itoh, Takaaki Yoshimasa, Tsunehisa Namba, Shuh Narumiya, Kazuwa Nakao

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Abstract

Background: Prostacyclin elicits a potent vasodilation and inhibition of platelet aggregation through binding to its membrane receptor. The impairment of prostacyclin receptor activity is implicated in various human cardiovascular diseases. In the present study, we succeeded in the isolation and characterization of human prostacyclin receptor cDNA and elucidated its gene expression in human tissues. Methods and Results: We isolated a cDNA clone encoding the human prostacyclin receptor from a human lung cDNA library. The isolated cDNA clone encodes a 386-amino acid protein with seven putative transmembrane domains, which belongs to the G protein-coupled receptor superfamily. [3H]iloprost, a prostacyclin receptor agonist, specifically bound to the receptor transiently expressed in COS-7 cells. The binding was inhibited in the rank order of iloprost=cicaprost, another prostacyclin receptor agonist, >prostaglandin E1 (PGE1)>>PGE2, PGF(2α), PGD2, STA2. In addition, iloprost dose-dependently stimulated cAMP generation in these COS-7 cells. These results are consistent with the characteristics of the human prostacyclin receptor. Northern blotting analysis on human tissues revealed that prostacyclin receptor mRNA is abundantly expressed in the aorta, lung, atrium, ventricle, and kidney. Conclusions: We cloned human prostacyclin receptor cDNA and elucidated its abundant gene expression in the human cardiovascular system. The present study will lead to better understanding of the significance of prostacyclin in humans and further facilitate the clinical application of prostacyclin.

Original languageEnglish
Pages (from-to)1643-1647
Number of pages5
JournalCirculation
Volume90
Issue number4 I
Publication statusPublished - 1994 Oct
Externally publishedYes

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Keywords

  • cDNA
  • cloning
  • mRNA
  • prostaglandins

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Nakagawa, O., Tanaka, I., Usui, T., Harada, M., Sasaki, Y., Itoh, H., Yoshimasa, T., Namba, T., Narumiya, S., & Nakao, K. (1994). Molecular cloning of human prostacyclin receptor cDNA and its gene expression in the cardiovascular system. Circulation, 90(4 I), 1643-1647.