E-Ring Isoprostane Augments Cholinergic Neurotransmission in Bovine Trachealis via FP Prostanoid Receptors

• Published in: American journal of respiratory cell and molecular biology Vol. 37; no. 6; pp. 739 - 747
• Main Authors: Paredes, Christine, Tazzeo, Tracy, Janssen, Luke J
• Format: Journal Article
• Language: English
• Published: United States Am Thoracic Soc 01-12-2007; American Thoracic Society
• Subjects: Acetylcholine - pharmacology; Animals; Cattle; Choline - metabolism; Dose-Response Relationship, Drug; In Vitro Techniques; Isoprostanes - pharmacology; Molecular Mimicry - drug effects; Muscle Contraction - drug effects; Muscle Relaxation - drug effects; Muscle, Smooth - cytology; Muscle, Smooth - drug effects; Neurons - drug effects; Neurons - metabolism; Receptors, Prostaglandin - agonists; Receptors, Prostaglandin - antagonists & inhibitors; Receptors, Prostaglandin - metabolism; Receptors, Thromboxane - agonists; Receptors, Thromboxane - antagonists & inhibitors; Synaptic Transmission - drug effects; Trachea - cytology; Trachea - drug effects; Trachea - metabolism
• ISSN: 1044-1549; 1535-4989
• DOI: 10.1165/rcmb.2007-0022OC

Isoprostanes are prostaglandin-like molecules that accumulate in oxidative stress and also exert powerful biological effects on a wide variety of tissues. We investigated the effects of several different isoprostanes on contractions evoked by electrical field stimulation (EFS) in bovine trachealis, finding only 15-E2t-IsoP to augment those responses. Many others have shown that isoprostanes act on prostanoid receptors, usually those of the thromboxane-selective prostanoid receptor (TP) subtype, although some describe actions through prostaglandin E2-selective prostanoid receptor (EP) or less frequently through prostaglandin F2alpha-selective prostanoid receptors (FP). We used an extensive panel of highly selective agonists and antagonists of prostanoid receptors to characterize the ones through which 15-E2t-IsoP was acting here. Pretreatment with the FP-selective AL-8810 significantly inhibited the augmentation, whereas TP- and EP-selective blockers did not. On the other hand, the augmentation exerted by 15-E2t-IsoP was mimicked by submicromolar concentrations of the FP-selective agonists PGF2alpha and fluprostenol, as well as by micromolar concentrations of the TP-selective agonist U46619. The concentration-response relationship for exogenously added acetylcholine was not significantly affected by 15-E2t-IsoP, confirming that the effect of the latter on EFS-evoked responses was exerted prejunctionally (i.e., to enhance release of Ach from nerve endings), rather than a direct postjunctional effect via a receptor on the smooth muscle. Finally, we investigated whether the inhibitory (adrenergic) innervation was also modulated by 15-E2t-IsoP, finding EFS-evoked relaxations to be unaffected by the isoprostane. We conclude that 15-E2t-IsoP acts upon an FP receptor on the cholinergic nerve endings, leading to enhanced neurotransmission.