Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2004-3-15
pubmed:abstractText
Recent studies in our lab and by others have indicated that cyclic ADP-ribose (cADPR) as a novel second messenger is importantly involved in vasomotor response in various vascular beds. However, the mechanism regulating cADPR production and actions remains poorly understood. The present study determined whether changes in redox status influence the production and action of cADPR in coronary arterial smooth muscle cells (CASMCs) and thereby alters vascular tone in these arteries. HPLC analyses demonstrated that xanthine (X, 40 microM)/xanthine oxidase (XO, 0.1 U/ml), a superoxide-generating system, increased the ADP-ribosyl cyclase activity by 59% in freshly isolated bovine CASMCs. However, hydrogen peroxide (H2O2, 1-100 microM) had no significant effect on ADP-ribosyl cyclase activity. In these CASMCs, X/XO produced a rapid increase in [Ca2+]i (Delta[Ca2+]i=201 nM), which was significantly attenuated by a cADPR antagonist, 8-Br-cADPR. Both inhibition of cADPR production by nicotinamide (Nicot) and blockade of Ca2+-induced Ca2+ release (CICR) by tetracaine (TC) and ryanodine (Rya) significantly reduced X/XO-induced rapid Ca2+ responses. In isolated, perfused, and pressurized small bovine coronary arteries, X at 2.5-80 microM with a fixed XO level produced a concentration-dependent vasoconstriction with a maximal decrease in arterial diameter of 45%. This X/XO-induced vasoconstriction was significantly attenuated by 8-Br-cADPR, Nicot, TC, or Rya. We conclude that superoxide activates cADPR production, and thereby mobilizes intracellular Ca2+ from the SR and produces vasoconstriction in coronary arteries.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0026-2862
pubmed:author
pubmed:issnType
Print
pubmed:volume
67
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
159-67
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:15020207-ADP-ribosyl Cyclase, pubmed-meshheading:15020207-Animals, pubmed-meshheading:15020207-Calcium Signaling, pubmed-meshheading:15020207-Cattle, pubmed-meshheading:15020207-Cells, Cultured, pubmed-meshheading:15020207-Chromatography, High Pressure Liquid, pubmed-meshheading:15020207-Coronary Vessels, pubmed-meshheading:15020207-Cyclic ADP-Ribose, pubmed-meshheading:15020207-Hydrogen Peroxide, pubmed-meshheading:15020207-Muscle, Smooth, Vascular, pubmed-meshheading:15020207-Myocytes, Smooth Muscle, pubmed-meshheading:15020207-Niacinamide, pubmed-meshheading:15020207-Oxidative Stress, pubmed-meshheading:15020207-Ryanodine, pubmed-meshheading:15020207-Second Messenger Systems, pubmed-meshheading:15020207-Superoxides, pubmed-meshheading:15020207-Tetracaine, pubmed-meshheading:15020207-Vasoconstriction, pubmed-meshheading:15020207-Xanthine Oxidase
pubmed:year
2004
pubmed:articleTitle
Enhanced production and action of cyclic ADP-ribose during oxidative stress in small bovine coronary arterial smooth muscle.
pubmed:affiliation
Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't