Regulation of the novel Mg2+ transporter transient receptor potential melastatin 7 (TRPM7) cation channel by bradykinin in vascular smooth muscle cells

Abstract

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.

Effects of Serum Amyloid A and Lysophosphatidylcholine on Intracellular Calcium Concentration in Human Coronary Artery Smooth Muscle Cells

“…The activation of TRPM7 induced by other substances such as dimethylphytosphingosine and bradykinin has been reported in U937 monocytes and vascular smooth muscle cells. 29,41) The plasma level of SAA in healthy subjects without acute inflammation is approximately 2-4 μg/mL or less. On the other hand, it may be increased by as much as 1000-fold above its baseline levels, reaching a concentration of 80 µM in acute inflammation recognized as a hallmark of atherosclerotic lesion.…”

“…41) Cells were loaded with mag-fura-2 AM (4 μM), which was dissolved in dimethyl sulfoxide with 0.02% pluronic acid. After mag-fura-2 loading, cells were isolated with 0.25% trypsin and diluted into 10 5 cells/mL Tyrode without Mg 2+ and with 0.1 mM EDTA.…”

2-Aminoethyl diphenyl borinate (2-APB) inhibits TRPM7 channels through an intracellular acidification mechanism

“…Human leukemic Jurkat T lymphocytes were the kind gift of Dr T. L. Brown, Wright State University. Cells were Mg 2+ influx was reduced by 10 μM 2-APB, 20 a concentration that neither blocked TRPM7 channels nor measurably acidified Jurkat T cells (see Figs. 1 and 3).…”

“…Thus, TRPC3, TRPC5, TRPC6, TRPM2, TRPM3 and TRPM7 are blocked by 2-APB at micromolar concentrations. 1,[13][14][15][16][17][18][19][20] In addition to its inhibitory actions, 2-APB activates several ion channels, which include Orai3 store-operated Ca 2+ channel (e.g., refs. 8 and 21), TRPV1, TRPV2, TRPV3 16,22 and TRPM6.…”

Molecular identification of ancient and modern mammalian magnesium transporters

“…Angiotensin II (59), aldosterone (77), bradykinin (9,104,177), epidermal growth factor (149), thrombin, (147), estrogen (48), metabolic acidosis/alkalosis (54, 82, 100), thiazide diuretics (101), the immunosuppressants tacrolimus (99) and cyclosporin A (69), and mechano-or osmo-induced stretch (4, 53, 102) have been implicated in alteration of TRPM7 and/or TRPM6 in a variety of cells. These changes may be mediated by covalent means, such as PLC-coupled receptors (77), or through controls at the transcript or protein level (49, 101,116,156).…”