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Nitric oxide inhibits Ca(2+) mobilization through cADP-ribose signaling in coronary arterial smooth muscle cells. Am J Physiol Heart Circ Physiol 2000 Sep;279(3):H873-81



Pubmed ID




Scopus ID

2-s2.0-0033826526   50 Citations


The present study was designed to determine whether the cADP-ribose-mediated Ca(2+) signaling is involved in the inhibitory effect of nitric oxide (NO) on intracellular Ca(2+) mobilization. With the use of fluorescent microscopic spectrometry, cADP-ribose-induced Ca(2+) release from sarcoplasmic reticulum (SR) of bovine coronary arterial smooth muscle cells (CASMCs) was determined. In the alpha-toxin-permeabilized primary cultures of CASMCs, cADP-ribose (5 microM) produced a rapid Ca(2+) release, which was completely blocked by pretreatment of cells with the cADP-ribose antagonist 8-bromo-cADP-ribose (8-Br-cADPR). In intact fura 2-loaded CASMCs, 80 mM KCl was added to depolarize the cells and increase intracellular Ca(2+) concentration ([Ca(2+)](i)). Sodium nitroprusside (SNP), an NO donor, produced a concentration-dependent inhibition of the KCl-induced increase in [Ca(2+)](i), but it had no effect on the U-46619-induced increase in [Ca(2+)](i). In the presence of 8-Br-cADPR (100 microM) and ryanodine (10 microM), the inhibitory effect of SNP was markedly attenuated. HPLC analyses showed that CASMCs expressed the ADP-ribosyl cyclase activity, and SNP (1-100 microM) significantly reduced the ADP-ribosyl cyclase activity in a concentration-dependent manner. The effect of SNP was completely blocked by addition of 10 microM oxygenated hemoglobin. We conclude that ADP-ribosyl cyclase is present in CASMCs, and NO may decrease [Ca(2+)](i) by inhibition of cADP-ribose-induced Ca(2+) mobilization.

Author List

Yu JZ, Zhang DX, Zou AP, Campbell WB, Li PL


William B. Campbell PhD Chair, Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin
David X. Zhang MD, PhD Associate Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

ADP-ribosyl Cyclase
ADP-ribosyl Cyclase 1
Adenosine Diphosphate Ribose
Antigens, CD
Antigens, Differentiation
Cell Membrane Permeability
Cells, Cultured
Coronary Vessels
Cyclic ADP-Ribose
Guanylate Cyclase
Muscle, Smooth, Vascular
NAD+ Nucleosidase
Nitric Oxide
Nucleotides, Cyclic
Potassium Chloride
Sarcoplasmic Reticulum
Signal Transduction
Type C Phospholipases
Vasoconstrictor Agents
Vasodilator Agents
jenkins-FCD Prod-482 91ad8a360b6da540234915ea01ff80e38bfdb40a