Effect of 8-iso-prostaglandin F2-ALFA on acetylcholine release from parasympathetic nerves in guinea pig airways

8-Iso-prostaglandin F2α is present in increased amounts in airway inflammation. 8-Iso-prostaglandin F2α constricts the airways via the activation of thromboxane A2 receptors. However, thromboxane A2 receptors are also present pre-junctionally on cholinergic nerve terminals innervating guinea pig trachea. We have demonstrated that 8-iso-prostaglandin F2α inhibited electrical field stimulation-evoked [3H]acetylcholine release in a concentration-dependent manner, an effect that was not inhibited by the selective thromboxane A2 receptor antagonist {4(Z)-6-[(2,4,5cis)2-(2-chlorophenyl)-4-(2-hydroxyphenyl)1,3-dioxan- 5-yl]hexenoic acid} (ICI 192,605). These data suggest that 8-iso-prostaglandin F2α inhibits acetylcholine release through a receptor distinct from the thromboxane A2 receptor and provides evidence that isoprostanes may have a 'dual' role as both beneficial and deleterious mediators in airway disease.