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J. Biol. Chem., Vol. 278, Issue 47, 46387-46395, November 21, 2003

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A New Peptidic Ligand and Its Receptor Regulating Adrenal Function in Rats^*

Shoji Fukusumi, Hiromi Yoshida, Ryo Fujii, Minoru Maruyama, Hidetoshi Komatsu, Yugo Habata, Yasushi Shintani, Shuji Hinuma, and Masahiko Fujino

From the Discovery Research Laboratories, Pharmaceutical Research Division, Takeda Chemical Industries Ltd., Wadai 10 Tsukuba, Ibaraki, 300-4293 Japan

We searched for peptidic ligands for orphan G protein-coupled receptors utilizing a human genome data base and identified a new gene encoding a preproprotein that could generate a peptide. This peptide consisted of 43 amino acid residues starting from N-terminal pyroglutamic acid and ending at C-terminal arginine-phenylalanine-amide. We therefore named it QRFP after pyroglutamylated arginine-phenylalanine-amide peptide. We subsequently searched for its receptor and found that Chinese hamster ovary cells expressing an orphan G protein-coupled receptor, AQ27, specifically responded to QRFP. We analyzed tissue distributions of QRFP and its receptor mRNAs in rats utilizing quantitative reverse transcription-polymerase chain reaction and in situ hybridization. QRFP mRNA was highly expressed in the hypothalamus, whereas its receptor mRNA was highly expressed in the adrenal gland. The intravenous administration of QRFP caused the release of aldosterone, suggesting that QRFP and its receptor have a regulatory function in the rat adrenal gland.

Received for publication, May 20, 2003 , and in revised form, September 5, 2003.

The nucleotide sequence(s) reported in this paper has been submitted to the DDBJ/GenBank^TM/EBI Data Bank with accession number(s) AB109625, AB109626, AB109627, AB109628, AB109629, AB109630, and AB109631.

^* The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article (available at http://www.jbc.org) contains Supplemental Figs. 1–3.

Both authors contributed equally to this work.

To whom correspondence should be addressed. Tel.: 81-29-864-5035; Fax: 81-29-864-5000; E-mail: Hinuma_Shuji{at}takeda.co.jp.

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