Tumor necrosis factor-alpha downregulates adrenomedullin receptors in human coronary artery smooth muscle cells.
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.
Nagoshi
Yasuko
Y
First Department of Internal Medicine, Miyazaki Medical College, University of Miyazaki, 5200 Kihara, Kiyotake, 889-1692, Japan.
Kuwasako
Kenji
K
Cao
Yuan-Ning
YN
Imamura
Takuroh
T
Kitamura
Kazuo
K
Eto
Tanenao
T
D058286:Calcitonin Receptor-Like Protein; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000166:cytology*; D015536:Down-Regulation / Q000187:drug effects*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000378:metabolism; D058262:Receptor Activity-Modifying Protein 1; D058263:Receptor Activity-Modifying Protein 2; D058261:Receptor Activity-Modifying Proteins; D058265:Receptors, Adrenomedullin; D018003:Receptors, Calcitonin / Q000235:genetics / Q000378:metabolism; D018000:Receptors, Peptide / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
C545578:CALCRL protein, human; D058286:Calcitonin Receptor-Like Protein; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C545502:RAMP1 protein, human; C545503:RAMP2 protein, human; D058262:Receptor Activity-Modifying Protein 1; D058263:Receptor Activity-Modifying Protein 2; D058261:Receptor Activity-Modifying Proteins; D058265:Receptors, Adrenomedullin; D018003:Receptors, Calcitonin; D018000:Receptors, Peptide; D014409:Tumor Necrosis Factor-alpha