Role of ADP-ribose in 11,12-EET-induced activation of KCa channels in coronary arterial smooth muscle cells

Pin Lan Li*, David X. Zhang, Zhi-Dong Ge, William B. Campbell

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

38 Scopus citations

Abstract

We recently reported that cADP-ribose (cADPR) and ADP-ribose (ADPR) play an important role in the regulation of the Ca2+-activated K+ (KCa) 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 KCa 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·min-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 KCa channel activity by 5.6-fold. The NAD glycohydrolase inhibitor cibacron blue 3GA (3GA, 100 μM) significantly attenuated 11,12-EET-induced increase in the KCa channel activity in CASMCs. However, 3GA had no effect on the KCa 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 μM) 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 KCa channels in CASMCs and consequently results in vasodilation of coronary artery.

Original languageEnglish (US)
Pages (from-to)H1229-H1236
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume282
Issue number4 51-4
DOIs
StatePublished - 2002

Keywords

  • Endothelium-derived hyperpolarization factor
  • Epoxyeicosatrienoic acid
  • K channels
  • Nicotinamide adenine dinucleotide glycohydrolase

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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