Article: Regulation of the novel Mg2+ transporter transient receptor potential melastatin 7 (TRPM7) cation channel by bradykinin in vascular smooth muscle cells.
2008 Volume 27, Issue 1, Page(s) 155–166
Abstract: Background: Transient receptor potential melastatin 7 (TRPM7) channels have been identified ... of annexin-1 (TRPM7 substrate) and increases transmembrane Mg2+ transport and vascular smooth muscle cell ... receptor; and bradykinin regulates VSMC [Mg2+]i and migration through TRPM7. These data identify TRPM7 ...
| Abstract | Background: Transient receptor potential melastatin 7 (TRPM7) channels have been identified in the vasculature. However, their regulation and function remain unclear. Methods: Here, we tested the hypothesis that bradykinin and its second messenger cAMP upregulate TRPM7, which stimulates activation of annexin-1 (TRPM7 substrate) and increases transmembrane Mg2+ transport and vascular smooth muscle cell (VSMC) migration. Human and rat VSMCs were studied. TRPM7 phosphorylation was assessed by immunoprecipitation:immunoblotting using antiphospho-serine/threonine and anti-TRPM7 antibodies. [Mg2+]i was measured by mag-fura-2. TRPM7 was downregulated by small interfering RNA and 2-aminoethoxydiphenyl borate. Annexin-1 activity was assessed by cytosol-to-membrane translocation. Cell migration and invasion, functional responses to bradykinin, were assessed in transwell chambers. Results: Bradykinin increased expression of TRPM7 and annexin-1. TRPM7 was rapidly (5 min) phosphorylated on serine/threonine but not on tyrosine residues by bradykinin. [Mg2+]i was increased in bradykinin-stimulated cells (0.53 versus 0.68 mmol/l, basal versus bradykinin, P < 0.01). Annexin-1 activation was increased by bradykinin and inhibited by 2-aminoethoxydiphenyl borate. Although Hoe 140 (B2 receptor antagonist), U-73122 (phospholipase C inhibitor), 4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine (c-Src inhibitor) and chelerythrine (protein kinase C inhibitor) blocked bradykinin actions, dibutyryl-c-AMP was without effect. In small interfering RNA-transfected and in 2-aminoethoxydiphenyl borate-treated cells, bradykinin-induced Mg2+ influx and VSMC migration were reduced. Conclusion: Our results demonstrate that bradykinin regulates TRPM7 and its downstream target annexin-1 through phospholipase C-dependent, protein kinase C-dependent and c-Src-dependent and cAMP-independent pathways; effects are mediated through bradykinin type 2 receptor; and bradykinin regulates VSMC [Mg2+]i and migration through TRPM7. These data identify TRPM7/annexin-1/Mg2+ as a novel pathway in bradykinin signaling. |
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| MeSH term(s) | Animals ; Annexin A1/metabolism ; Bradykinin/pharmacology ; Cell Movement/drug effects ; Cells, Cultured ; Cyclic AMP/physiology ; Humans ; Ion Transport/drug effects ; Magnesium/metabolism ; Muscle, Smooth, Vascular/cytology ; Muscle, Smooth, Vascular/metabolism ; Myocytes, Smooth Muscle/metabolism ; Phosphorylation ; Protein-Serine-Threonine Kinases ; Rats ; Rats, Inbred WKY ; Receptor, Bradykinin B2/physiology ; TRPM Cation Channels/physiology | ||||||||||
| Chemical Substances | Annexin A1 ; Receptor, Bradykinin B2 ; TRPM Cation Channels ; Cyclic AMP (E0399OZS9N) ; Protein-Serine-Threonine Kinases (EC 2.7.11.1) ; TRPM7 protein, human (EC 2.7.11.1) ; Magnesium (I38ZP9992A) ; Bradykinin (S8TIM42R2W) | ||||||||||
| Language | English | ||||||||||
| Publishing date | 2008-11-24 | ||||||||||
| Publishing country | England | ||||||||||
| Document type | Journal Article ; Research Support, Non-U.S. Gov't | ||||||||||
| ZDB-ID | 605532-1 | ||||||||||
| ISSN | 1473-5598 ; 0263-6352 ; 0952-1178 | ||||||||||
| ISSN (online) | 1473-5598 | ||||||||||
| ISSN | 0263-6352 ; 0952-1178 | ||||||||||
| DOI | 10.1097/hjh.0b013e3283190582 | ||||||||||
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| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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