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Role of ADP-ribose in 11,12-EET-induced activation of K(Ca) channels in coronary arterial smooth muscle cells. Am J Physiol Heart Circ Physiol 2002 Apr;282(4):H1229-36



Pubmed ID




Scopus ID

2-s2.0-0036084912   37 Citations


We recently reported that cADP-ribose (cADPR) and ADP-ribose (ADPR) play an important role in the regulation of the Ca(2+)-activated K(+) (K(Ca)) channel activity in coronary arterial smooth muscle cells (CASMCs). The present study determined whether these novel signaling nucleotides participate in 11,12-epoxyeicosatrienoic acid (11,12-EET)-induced activation of the K(Ca) channels in CASMCs. HPLC analysis has shown that 11,12-EET increased the production of ADPR but not the formation of cADPR. The increase in ADPR production was due to activation of NAD glycohydrolase as measured by a conversion rate of NAD into ADPR. The maximal conversion rate of NAD into ADPR in coronary homogenate was increased from 2.5 +/- 0.2 to 3.4 +/- 0.3 nmol*(-1) *mg protein(-1) by 11,12-EET. The regioisomers of 8,9-EET, 11,12-EET, and 14,15-EET also significantly increased ADPR production from NAD. Western blot analysis and immunoprecipitation demonstrated the presence of NAD glycohydrolase, which mediated 11,12-EET-activated production of ADPR. In cell-attached patches, 11,12-EET (100 nM) increases K(Ca) channel activity by 5.6-fold. The NAD glycohydrolase inhibitor cibacron blue 3GA (3GA, 100 microM) significantly attenuated 11,12-EET-induced increase in the K(Ca) channel activity in CASMCs. However, 3GA had no effect on the K(Ca) channels activity in inside-out patches. 11,12-EET produced a concentration-dependent relaxation of precontracted coronary arteries. This 11,12-EET-induced vasodilation was substantially attenuated by 3GA (30 microM) with maximal inhibition of 57%. These results indicate that 11,12-EET stimulates the production of ADPR and that intracellular ADPR is an important signaling molecule mediating 11,12-EET-induced activation of the K(Ca) channels in CASMCs and consequently results in vasodilation of coronary artery.

Author List

Li PL, Zhang DX, Ge ZD, Campbell WB


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

8,11,14-Eicosatrienoic Acid
Adenosine Diphosphate Ribose
Arachidonic Acid
Coronary Vessels
Hydroxyeicosatetraenoic Acids
In Vitro Techniques
Muscle, Smooth, Vascular
Patch-Clamp Techniques
Potassium Channels, Calcium-Activated
jenkins-FCD Prod-482 91ad8a360b6da540234915ea01ff80e38bfdb40a