Ca2+-independent phospholipase A2 is required for agonist-induced Ca2+ sensitization of contraction in vascular smooth muscle

Zhenheng Guo, Wen Su, Zhongmin Ma, George M. Smith, Ming C. Gong

Research output: Contribution to journalArticlepeer-review

51 Scopus citations

Abstract

Excitatory agonists can induce significant smooth muscle contraction under constant free Ca2+ through a mechanism called Ca2+ sensitization. Considerable evidence suggests that free arachidonic acid plays an important role in mediating agonist-induced Ca2+-sensitization; however, the molecular mechanisms responsible for maintaining and regulating free arachidonic acid level are not completely understood. In the current study, we demonstrated that Ca2+-independent phospholipase A2 (iPLA2) is expressed in vascular smooth muscle tissues. Inhibition of the endogenous iPLA2 activity by bromoenol lactone (BEL) decreases basal free arachidonic acid levels and reduces the final free arachidonic acid level after phenylephrine stimulation, without significant effect on the net increase in free arachidonic acid stimulated by phenylephrine. Importantly, BEL treatment diminishes agonist-induced Ca2+ sensitization of contraction from 49 ± 3.6 to 12 ± 1.0% (p < 0.01). In contrast, BEL does not affect agonist-induced diacylglycerol production or contraction induced by Ca2+, phorbol 12,13-dibutyrate (a protein kinase C activator), or exogenous arachidonic acid. Further, we demonstrate that adenovirus-mediated overexpression of exogenous iPLA2 in mouse portal vein tissue significantly potentiates serotonin-induced contraction. Our data provide the first evidenee that iPLA2 is required for maintaining basal free arachidonic acid levels and thus is essential for agonist-induced Ca2+-sensitization of contraction in vascular smooth muscle.

Original languageEnglish
Pages (from-to)1856-1863
Number of pages8
JournalJournal of Biological Chemistry
Volume278
Issue number3
DOIs
StatePublished - Jan 17 2003

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint

Dive into the research topics of 'Ca2+-independent phospholipase A2 is required for agonist-induced Ca2+ sensitization of contraction in vascular smooth muscle'. Together they form a unique fingerprint.

Cite this