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Abstract
We have shown that in bovine iris sphincter membranes G proteins are involved in coupling muscarinic-, PGF2α-, endothelin- and platelet-activating factor receptors to the activation of phospholipase A2 and the release of arachidonic acid. GTPγS and GTPγS plus carbachol stimulated arachidonic acid release in the membranes in a dose- and time-dependent manner. Nucleotide stimulation was specific to GTPγS, since GDP, GDPβS and ATP had no effect. The stimulatory effect of GTPγS plus carbachol was blocked by atropine and it required the presence of physiological concentrations of Ca2–. AIF4, which bypasses the receptor and directly activates the G protein, induced arachidonic acid liberation in the intact iris sphincter, but was ineffective in the membranes. Addition of GTPγS plus carbachol to sphincter muscle membranes prelabeled with [3H]inositol or 3H-arachidonic acid resulted in the formation of lysophosphatidylinositol and the liberation of arachidonic acid, thus suggesting the involvement of phospholipase A2.In vitro treatment of the iris membranes with pertussis toxic inhibited arachidonic acid release by the agonists. This is in contrast to the pertussis toxin-insensitive G protein that activates phospholipase C in this tissue (22). These data demonstrate that in the iris sphincter a G protein is involved in the step between receptor activation and the activation of phospholipase A2, and that arachidonic acid release in this tissue is mediated by a pertussis-toxin-sensitive G protein-coupled phospholipase A2. Thus, GTP can regulate arachidonic acid release and its subsequent conversion into eicosanoids by stimulating its formation.