Effect of 8-iso-prostaglandin F(2 alpha) on acetylcholine release from parasympathetic nerves in guinea pig airways.
8-Iso-prostaglandin F(2 alpha) is present in increased amounts in airway inflammation. 8-Iso-prostaglandin F(2 alpha) constricts the airways via the activation of thromboxane A(2) receptors. However, thromboxane A(2) receptors are also present pre-junctionally on cholinergic nerve terminals innervating guinea pig trachea. We have demonstrated that 8-iso-prostaglandin F(2 alpha) inhibited electrical field stimulation-evoked [3H]acetylcholine release in a concentration-dependent manner, an effect that was not inhibited by the selective thromboxane A(2) receptor antagonist 4(Z)-6-[(2,4,5 cis)2-(2-chlorophenyl)-4-(2-hydroxyphenyl)1,3-dioxan-5-yl]hexenoic acid (ICI 192,605). These data suggest that 8-iso-prostaglandin F(2 alpha) inhibits acetylcholine release through a receptor distinct from the thromboxane A(2) receptor and provides evidence that isoprostanes may have a 'dual' role as both beneficial and deleterious mediators in airway disease.
Spicuzza
L
L
Institute of Respiratory Diseases, University of Catania, Italy.
Barnes
P J
PJ
Di Maria
G U
GU
Belvisi
M G
MG
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D015237:Dinoprost / Q000031:analogs & derivatives / Q000494:pharmacology*; D004146:Dioxanes / Q000494:pharmacology; D004558:Electric Stimulation; D028441:F2-Isoprostanes; D006168:Guinea Pigs; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism; D010275:Parasympathetic Nervous System / Q000187:drug effects* / Q000378:metabolism; D017482:Receptors, Thromboxane / Q000819:agonists / Q000037:antagonists & inhibitors; D014132:Trachea / Q000294:innervation*; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D004146:Dioxanes; D028441:F2-Isoprostanes; D017482:Receptors, Thromboxane; D014662:Vasoconstrictor Agents; C057498:ICI 192605; C075750:8-epi-prostaglandin F2alpha; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D015237:Dinoprost; D000109:Acetylcholine