Abstract:
: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.
journal_name
Am J Respir Cell Mol Biolauthors
Paredes C,Tazzeo T,Janssen LJdoi
10.1165/rcmb.2007-0022OCsubject
Has Abstractpub_date
2007-12-01 00:00:00pages
739-47issue
6eissn
1044-1549issn
1535-4989pii
2007-0022OCjournal_volume
37pub_type
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