RGD Reference Report - Calcium-independent phospholipase A(2)-derived arachidonic acid is essential for endothelium-dependent relaxation by acetylcholine. - Rat Genome Database

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Calcium-independent phospholipase A(2)-derived arachidonic acid is essential for endothelium-dependent relaxation by acetylcholine.

Authors: Seegers, HC  Gross, RW  Boyle, WA 
Citation: Seegers HC, etal., J Pharmacol Exp Ther. 2002 Sep;302(3):918-23.
RGD ID: 6482758
Pubmed: PMID:12183647   (View Abstract at PubMed)

The role of calcium-independent phospholipase A(2) (iPLA(2))-produced arachidonic acid (AA) in acetylcholine (ACh)-mediated, endothelium-dependent vascular relaxation was investigated. ACh-induced relaxation of phenylephrine-constricted isolated rat mesenteric resistance arteries was attenuated following pretreatment with (E)-6-(bromomethylene)tetrahydro-3-(1-naphthalenyl)-2H-pyran-2-one (BEL; 1 microM; p < 0.01), a highly selective suicide substrate inhibitor of iPLA(2). Following BEL, the ACh relaxation could be completely restored following pretreatment with picomolar quantities of the cell-permeant methyl ester analog of AA (arachidonic acid methyl ester, AA-Me). Higher amounts of AA-Me (1 microM) had a direct endothelium-dependent relaxing action, which was inhibited by the nitric-oxide synthase inhibitor (N(omega)-nitro-L-arginine; 100 microM), independent of ACh, and unaffected by BEL. Neither the ACh relaxation restoring action nor the direct relaxing action of AA-Me was affected by preincubation with inhibitors of the lipoxygenase (esculetin, 10 microM) or cytochrome P450 monooxygenase (17-octadecynoic acid; 10 microM) pathways; and both actions of AA-Me were enhanced following preincubation with the cyclooxygenase inhibitor indomethacin (10 microM; p < 0.05). The results of the present study indicate that iPLA(2)-produced AA plays an essential role in ACh-mediated endothelium-dependent relaxation in rat mesenteric resistance arteries.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
vasodilation  IMP 6482758 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Pla2g6  (phospholipase A2 group VI)


Additional Information