Low [Mg(2+)](o) induces contraction and [Ca(2+)](i) rises in cerebral arteries: roles of ca(2+), PKC, and PI3.
Removal of extracellular Ca(2+) concentration ([Ca(2+)](o)) and pretreatment of canine basilar arterial rings with either an antagonist of voltage-gated Ca(2+) channels (verapamil), a selective antagonist of the sarcoplasmic reticulum Ca(2+) pump [thapsigargin (TSG)], caffeine plus a specific antagonist of ryanodine-sensitive Ca(2+) release (ryanodine), or a D-myo-inositol 1,4,5-trisphosphate [Ins(1,4,5)P(3)]- mediated Ca(2+) release antagonist (heparin) markedly attenuates low extracellular Mg(2+) concentration ([Mg(2+)](o))-induced contractions. Low [Mg(2+)](o)-induced contractions are significantly inhibited by pretreatment of the vessels with Gö-6976 [a protein kinase C-alpha (PKC-alpha)- and PKC-betaI-selective antagonist], bisindolylmaleimide I (Bis, a specific antagonist of PKC), and wortmannin or LY-294002 [selective antagonists of phosphatidylinositol-3 kinases (PI3Ks)]. These antagonists were also found to relax arterial contractions induced by low [Mg(2+)](o) in a concentration-dependent manner. The absence of [Ca(2+)](o) and preincubation of the cells with verapamil, TSG, heparin, or caffeine plus ryanodine markedly attenuates the transient and sustained elevations in the intracellular Ca(2+) concentration ([Ca(2+)](i)) induced by low-[Mg(2+)](o) medium. Low [Mg(2+)](o)-produced increases in [Ca(2+)](i) are also suppressed markedly in the presence of Gö-6976, Bis, wortmannin, or LY-294002. The present study suggests that both Ca(2+) influx through voltage-gated Ca(2+) channels and Ca(2+) release from intracellular stores [both Ins(1,4,5)P(3) sensitive and ryanodine sensitive] play important roles in low-[Mg(2+)](o) medium-induced contractions of isolated canine basilar arteries. Such contractions are clearly associated with activation of PKC isoforms and PI3Ks.
Yang
Z W
ZW
Department of Physiology and Pharmacology, Health Science Center at Brooklyn, State University of New York, Brooklyn, New York 11203, USA.
Wang
J
J
Zheng
T
T
Altura
B T
BT
Altura
B M
BM
D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology; D001488:Basilar Artery / Q000201:enzymology*; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002227:Carbazoles / Q000494:pharmacology; D002867:Chromones / Q000494:pharmacology; D004285:Dogs; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005110:Extracellular Space / Q000378:metabolism; D006493:Heparin / Q000494:pharmacology; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D008274:Magnesium / Q000378:metabolism / Q000494:pharmacology*; D008301:Maleimides / Q000494:pharmacology; D009025:Morpholines / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000201:enzymology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012433:Ryanodine / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D019284:Thapsigargin / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*; D000077191:Wortmannin
D000730:Androstadienes; D000925:Anticoagulants; D002110:Caffeine; D002118:Calcium; D002227:Carbazoles; D002867:Chromones; D004791:Enzyme Inhibitors; D006493:Heparin; D007211:Indoles; D008274:Magnesium; D008301:Maleimides; D009025:Morpholines; D019869:Phosphatidylinositol 3-Kinases; D010726:Phosphodiesterase Inhibitors; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011493:Protein Kinase C; D012433:Ryanodine; D019284:Thapsigargin; D000077191:Wortmannin; C081021:Go 6976; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C088060:bisindolylmaleimide