Phospholipid‐Derived Second Messengers

Exton, John H.

doi:10.1002/cphy.cp070111

Cited by 2 publications

(1 citation statement)

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“…In light of this evidence from both functional studies and biochemical measurements, we conclude that H 2 O 2 -induced stimulation of BK Ca channel activity involves PLA 2 activity and release of AA from membrane lipids in coronary artery smooth muscle. PLA 2 has been classified as either secretory or cytosolic, and evidence indicates that the cytosolic form is the agonist-stimulated PLA 2 (10), which is also stimulated by H 2 O 2 in endothelial (3) or aortic smooth muscle cells (28).…”

Section: Discussionmentioning

confidence: 99%

H₂O₂opens BK_Cachannels via the PLA₂-arachidonic acid signaling cascade in coronary artery smooth muscle

Barlow

El‐Mowafy

White

2000

American Journal of Physiology-Heart and Circulatory Physiology

101

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H(2)O(2) is a reactive oxygen species that contracts or relaxes vascular smooth muscle, but the molecular basis of these effects remains obscure. We previously demonstrated that H(2)O(2) opens the large-conductance, calcium- and voltage-activated (BK(Ca)) potassium channel of coronary myocytes (2) and now report physiological and biochemical evidence that the effect of H(2)O(2) on coronary smooth muscle involves the phospholipase A(2) (PLA(2))/arachidonic acid (AA) signaling cascades. H(2)O(2) stimulation of BK(Ca) channel activity was inhibited by arachidonyl trifluoromethyl ketone, an inhibitor of cytosolic PLA(2). Furthermore, H(2)O(2) stimulated release of [(3)H]AA from coronary myocytes, and exogenous AA mimicked the effect of H(2)O(2) on BK(Ca) channels. Inhibitors of protein kinase C activity attenuated the effect of H(2)O(2) on BK(Ca) channels, [(3)H]AA release, or intact coronary arteries. In addition, the effect of H(2)O(2) or AA on BK(Ca) channels was inhibited by blockers of lipoxygenase metabolism. In contrast, inhibitors of cyclooxygenase or cytochrome P-450 had no effect. We propose that H(2)O(2) relaxes coronary arteries by stimulating BK(Ca) channels via the PLA(2)/AA signaling cascade and that lipoxygenase metabolites mediate this response.

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Section: Discussionmentioning

confidence: 99%