کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
9884437 | 1536794 | 2005 | 7 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Identification of MrgX2 as a human G-protein-coupled receptor for proadrenomedullin N-terminal peptides
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
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چکیده انگلیسی
Proadrenomedullin N-terminal 20 peptide (PAMP[1-20]/PAMP-20) and its truncated analog, PAMP[9-20]/PAMP-12, are endogenous peptides that elicit hypotension through inhibiting catecholamine secretion from sympathetic nerve endings and adrenal chromaffin cells. Although the binding sites for PAMP are widely distributed, the nature of its receptor has been elusive. In an effort to identify potential PAMP receptor(s), we found that a human G-protein-coupled receptor, MrgX2, was specifically activated by PAMP. Although a previous study revealed that MrgX2 was a receptor for cortistatin, a neuropeptide involved in sleep regulation and locomotor activity, our present data indicated that the rank order of the agonistic effect against MrgX2 was “PAMP-12 â¥Â cortistatin > PAMP-20”. These activities were confirmed by the inhibition of the forskolin-elevated cAMP accumulation, Ca2+ mobilization, and [35S]guanosine 5â²-(γ-thio)triphosphate binding assays. These findings suggest that MrgX2 couples with not only Gαq but also Gαi, consistent with previous reports on the pharmacological profile of PAMP signaling. Furthermore, by immunostaining, we found that MrgX2 was expressed in the adrenal chromaffin cells as well as the dorsal root ganglia. From these results, we concluded that MrgX2 is a potential human PAMP-12 receptor that regulates catecholamine secretion from adrenal glands. The present discovery will eventually lead to a better understanding of the pathophysiological role of proadrenomedullin peptides.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical and Biophysical Research Communications - Volume 330, Issue 4, 20 May 2005, Pages 1146-1152
Journal: Biochemical and Biophysical Research Communications - Volume 330, Issue 4, 20 May 2005, Pages 1146-1152
نویسندگان
Masazumi Kamohara, Ayako Matsuo, Jun Takasaki, Masanobu Kohda, Mitsuyuki Matsumoto, Shun-ichiro Matsumoto, Takatoshi Soga, Hideki Hiyama, Masato Kobori, Masao Katou,