Effect of Nitric Oxide on Arachidonic Acid Release from Human Amnion-like WISH Cells

In order to clarify the possible interactions between nitric oxide (NO) and arachidonic acid (AA) pathways, human amnion-like WISH cells were perifused to measure the effects of the following substances on [3H]arachidonic acid release: (1) sodium nitroprusside (SNP), a nitric oxide donor; (2) 1,1,1-trifluoromethyl-6,9,12,15-heicosatetraen-2-one, a cytosolic phospholipase A2(cPLA2) inhibitor; (3)l-arginine, the substrate of nitric oxide synthase (NOS); (4) 3-(5′-Hydroxymethyl-2′-furyl)-1-benzylindazole and 1H-[1,2,4]oxadiazolo[4,3-α]quinoxalin-1-one, activator and inhibitor of soluble guanylyl cyclase, respectively; (5) a membrane-permeable non-hydrolyzable analogue of guanosine-3′,5′-cyclic monophosphate (cGMP). Furthermore, the effect of SNP on prostaglandin E2(PGE2) release was tested. Exogenous and endogenous NO, as well as the guanylyl cyclase activator and cGMP analogue, significantly increased [3H]arachidonic acid release. Both soluble guanylyl cyclase and PLA2inhibitors counteracted SNP response. Exogenous NO increased PGE2release, although to a much lesser degree compared with arachidonic acid release.