Biochemical and Biophysical Research Communications
Identification of MrgX2 as a human G-protein-coupled receptor for proadrenomedullin N-terminal peptides☆
Section snippets
Materials and methods
Materials. Human PAMP-12 and PAMP-20 were purchased from the Peptide Institute (Osaka, Japan). Human cortistatin (CST-14) and BAM-22P were from Phoenix Pharmaceutical (Belmont, CA, USA) and Bachem (Bubendorf, Switzerland), respectively. 3-Isobutyl-1-methylxanthine (IBMX), pertussis toxin (PTX), and guanosine 5′-diphosphate (GDP) were from Sigma (St. Louis, MO, USA). Forskolin and methotrexate were from Wako (Osaka, Japan). [35S]guanosine 5′-(γ-thio)triphosphate ([35S]GTPγS) (1000 Ci/mmol) was
PAMP-12 specifically responds to MrgX2
Previous studies revealed that it is possible for a presumed PAMP receptor(s) to be a Gαi/o-protein-coupled receptor [16], [17], [18]. Therefore, based on the change in intracellular cAMP, we have searched for a PAMP-responsive receptor(s) from each type of orphan GPCR-expressing cell. By exploring these potential sources, we found that CHO cells stably expressing MrgX2 were specifically activated by PAMP-12 (Fig. 1A). MrgX2 has been classified as a member of the GPCR subfamily referred to as
Discussion
The proadrenomedullin gene products, PAMP-12 and PAMP-20, act as circulating hormones with hypotensive activities. Clinically, plasma levels of PAMP have been reported to increase in patients with a variety of diseases such as essential hypertension [28], chronic renal failure [29], congestive heart failure [30], and chronic glomerulonephritis [31]. This suggests that the vasophysiological function of PAMP relates to many diseases. Although clinical evidence indicates the importance of PAMP
Acknowledgments
We thank Dr. Shigekazu Nagata for providing pEF-BOS, and Ms. Mariko Isshiki, Ms. Akiko Wakita, and Mr. Hideki Miyamoto for excellent technical assistance.
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Abbreviations: GPCR, G-protein-coupled receptor; PAMP, proadrenomedullin N-terminal peptide; AM, adrenomedullin; CST, cortistatin; Mrg, Mas-related gene; PTX, pertussis toxin; GTPγS, guanosine 5′-(γ-thio)triphosphate; DRG, dorsal root ganglia; EC50, median effective concentration.
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These authors contributed equally to this work.