title: Extracellular magnesium deficiency induces contraction of arterial muscle: role of PI3-kinases and MAPK signaling pathways.
abstract: The present study investigated the actions of extracellular Mg2+ ([Mg2+]o) deficiency on isolated rat aortae and rat aortic smooth muscle cells (RASMC). Exposure of isolated, intact rat aortic rings to Mg(2+)-free or Mg(2+)-deficient medium (0.15-0.6 mM) produced endothelium-independent, concentration-dependent contractions: the lower the [Mg2+]o, the stronger the contraction. Pre- or post-incubation of the vessels with low concentrations of U0126, SB-203580, PD-98059, wortmannin, LY-294002, or a SH2 domain inhibitor peptide suppressed [Mg2+]o deficiency-induced contractions significantly. The concentrations of these antagonists required for half-maximal inhibition (IC50) were not very different from the inhibitory constants (Ki) for these drugs. A variety of specific pharmacological antagonists of several known endogenously-formed vasoconstrictors did not inhibit or attenuate the contractions induced by low [Mg2+]o. Mg(2+)-free medium induced a 6- to 7-fold increase in intracellular Ca2+ ([Ca2+]i) in RASMC. Pre- or post-treatment of the cells with U0126, SB-203580, PD-98059, wortmannin, LY-294002, or a SH2 domain inhibitor peptide markedly inhibited the increments in ([Ca2+]i) in RASMC induced by exposure to Mg(2+)-free medium. The present findings suggest that Mg(2+)-deficiency-induced contractions of rat aortae are associated with activation of several cellular signal pathways, such as mitogen-activated protein kinase, phosphatidylinositol-3 (PI3) kinases, and SH2 domain-containing proteins.
authors.affiliation: Department of Physiology, Box 31, State University of New York, Health Sciences Center at Brooklyn, 11203, USA.
authors.forename: Z
authors.initials: Z
authors.lastname: Yang
authors.forename: J
authors.initials: J
authors.lastname: Wang
authors.forename: B T
authors.initials: BT
authors.lastname: Altura
authors.forename: B M
authors.initials: BM
authors.lastname: Altura
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000502:physiology; D002118:Calcium / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D008275:Magnesium Deficiency / Q000201:enzymology / Q000503:physiopathology*; D008297:Male; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors / Q000502:physiology; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000201:enzymology / Q000503:physiopathology*; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010748:Phosphopeptides / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D002118:Calcium; D004791:Enzyme Inhibitors; D020929:Mitogen-Activated Protein Kinase Kinases; D020928:Mitogen-Activated Protein Kinases; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010748:Phosphopeptides; C404208:acetyl-phosphotyrosyl-phosphotyrosyl-phosphotyrosyl-isoleucyl-glutamic acid