Low extracellular Mg2+ contraction of arterial muscle: role of protein kinase C and protein tyrosine phosphorylation.
The effects of extracellular Mg2+ ion ([Mg2+]0) deficiency on basal tension of isolated rat aortae and rat aortic smooth muscle cell Ca2+ metabolism were investigated in the present study. The contractions of rat aortae induced by diverse concentrations of low [Mg2+]0 were potentiated, greatly, by removal of the endothelium or pre-incubation of intact rat aortic rings with L-N(G)-monomethyl-arginine (L-NMMA). [Mg2+]0 deficiency-induced contractions were inhibited, to different degrees, by pre-treatment of the vessels with low concentrations of Gö6976, bisindolymaleimide I, genistein or a combination of bisindolymaleimide I with genistein. IC50 levels found for these three agents were found to be not too different from Ki values for these drugs. Pre-treatment of rat aortic smooth muscle cells with Gö6976, bisindolymaleimide I, genistein or a combination of bisindolymaleimide I with genistein suppressed, significantly, or almost eliminated both the rapid and stable increments in [Ca2+]i induced by Mg2+-free medium. The present findings suggest that both protein kinase C and protein tyrosine phosphorylation appear to play important roles in Mg2+ deficiency-induced contractions of isolated rat aortic smooth muscle, most likely via phosphorylation of L-type Ca2+ channels.
Yang
Z W
ZW
Department of Physiology, State University of New York, Health Science Center at Brooklyn, 11203, USA.
Altura
B T
BT
Altura
B M
BM
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000502:physiology; D001158:Arteries / Q000187:drug effects* / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D002227:Carbazoles / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019833:Genistein / Q000494:pharmacology; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D008274:Magnesium / Q000494:pharmacology*; D008297:Male; D008301:Maleimides / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D051381:Rats; D017208:Rats, Wistar
D002227:Carbazoles; D004791:Enzyme Inhibitors; D007211:Indoles; D008301:Maleimides; D010750:Phosphoproteins; C081021:Go 6976; D019000:Phosphotyrosine; D019833:Genistein; D011505:Protein-Tyrosine Kinases; D011493:Protein Kinase C; D008274:Magnesium; C070515:bisindolylmaleimide I; D002118:Calcium