PGE₂ sensitizes cultured pulmonary vagal sensory neurons to chemical and electrical stimuli

Mediators of inflammation, such as PGE₂ 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 PGE₂-elicited airway hypersensitivity. However, whether PGE₂ acts directly on these sensory nerves is unclear. The present study aimed to investigate whether PGE₂ has direct potentiating effects on nodose and jugular pulmonary C neurons cultured from adult Sprague-Dawley rats and, if so, determine whether the EP₂ 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) PGE₂ pretreatment (1 μM) increased the whole cell current density elicited by capsaicin and phenylbiguanide, chemical agents known to stimulate pulmonary C fibers; 2) selective activation of the EP₂ prostanoid receptor by butaprost (3-10 μM) increased the whole cell current density elicited by capsaicin; and 3) PGE₂, as well as butaprost, increased the number of action potentials evoked by current injection. Therefore, we conclude that PGE₂ directly sensitizes vagal pulmonary C neurons to chemical and electrical stimulation. Furthermore, butaprost modulates the neurons in a manner similar to that of PGE₂, suggesting that the effects of PGE₂ are mediated, at least in part, through the EP₂ prostanoid receptor.