Circulation, Vol 90, 1643-1647, Copyright © 1994 by American Heart Association
O Nakagawa, I Tanaka, T Usui, M Harada, Y Sasaki, H Itoh, T Yoshimasa, T Namba, S Narumiya and K Nakao
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, PGF2 alpha, 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.
ARTICLES
Molecular cloning of human prostacyclin receptor cDNA and its gene expression in the cardiovascular system
Department of Medicine, Kyoto University Faculty of Medicine, Japan.
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