title: PGE(2) sensitizes cultured pulmonary vagal sensory neurons to chemical and electrical stimuli.
abstract: Mediators of inflammation, such as PGE(2), are known to sensitize the airways to inhaled irritants and circulating autacoids. Evidence from in vivo studies has shown the involvement of vagal pulmonary C-fiber afferents in the PGE(2)-elicited airway hypersensitivity. However, whether PGE(2) acts directly on these sensory nerves is unclear. The present study aimed to investigate whether PGE(2) has direct potentiating effects on nodose and jugular pulmonary C neurons cultured from adult Sprague-Dawley rats and, if so, determine whether the EP(2) prostanoid receptor is involved. Pulmonary neurons were identified by retrograde labeling with a fluorescent tracer 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate. Using perforated patch-clamp technique, our results showed that 1) PGE(2) pretreatment (1 microM) increased the whole cell current density elicited by capsaicin and phenylbiguanide, chemical agents known to stimulate pulmonary C fibers; 2) selective activation of the EP(2) prostanoid receptor by butaprost (3-10 microM) increased the whole cell current density elicited by capsaicin; and 3) PGE(2), as well as butaprost, increased the number of action potentials evoked by current injection. Therefore, we conclude that PGE(2) directly sensitizes vagal pulmonary C neurons to chemical and electrical stimulation. Furthermore, butaprost modulates the neurons in a manner similar to that of PGE(2), suggesting that the effects of PGE(2) are mediated, at least in part, through the EP(2) prostanoid receptor.
authors.affiliation: Department of Physiology, University of Kentucky Medical Center, Lexington, Kentucky 40536, USA.
authors.forename: Kevin
authors.initials: K
authors.lastname: Kwong
authors.forename: Lu-Yuan
authors.initials: LY
authors.lastname: Lee
mesh_terms: D000527:Alprostadil / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D001980:Bronchi / Q000294:innervation; D002232:Carbocyanines; D002478:Cells, Cultured; D015232:Dinoprostone / Q000494:pharmacology*; D004558:Electric Stimulation; D005456:Fluorescent Dyes; D008168:Lung / Q000294:innervation*; D008297:Male; D009475:Neurons, Afferent / Q000187:drug effects* / Q000502:physiology*; D018408:Patch-Clamp Techniques; D011459:Prostaglandins E, Synthetic / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013268:Stimulation, Chemical; D014630:Vagus Nerve / Q000187:drug effects* / Q000502:physiology*
chemical_list: D002232:Carbocyanines; D005456:Fluorescent Dyes; D011459:Prostaglandins E, Synthetic; C024286:3,3'-dioctadecylindocarbocyanine; D000527:Alprostadil; C048491:butaprost; D015232:Dinoprostone