Tumor necrosis factor-alpha downregulates adrenomedullin receptors in human coronary artery smooth muscle cells |
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Authors: | Nagoshi Yasuko Kuwasako Kenji Cao Yuan-Ning Imamura Takuroh Kitamura Kazuo Eto Tanenao |
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Institution: | First Department of Internal Medicine, Miyazaki Medical College, University of Miyazaki, 5200 Kihara, Kiyotake, 889-1692, Japan. |
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Abstract: | We examined the effects of tumor necrosis factor (TNF)-alpha on the expression and functionality of adrenomedullin (AM) receptors in cultured human coronary artery smooth muscle cells. Analysis of real-time quantitative polymerase chain reactions showed that these cells abundantly express two AM receptors comprised of calcitonin receptor-like receptor (CRLR) and receptor activity-modifying protein 1 (RAMP1) or RAMP2. TNF-alpha induced time- and dose-dependent decreases in the expression of CRLR and RAMP1/2 mRNAs, thereby diminishing AM-evoked cAMP production. The suppression of these three mRNAs was unaffected by inhibiting NOS, protein kinase G, protein kinase A, superoxide formation or NF-kappaB activation. |
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