Prostaglandin E 2 ‐induced modification of tetrodotoxin‐resistant Na + currents involves activation of both EP 2 and EP 4 receptors in neonatal rat nodose ganglion neurones

1 The aim of the present study was to investigate which EP receptor subtypes (EP 1 –EP 4 ) act predominantly on the modification of the tetrodotoxin‐resistant Na + current ( I NaR ) in acutely isolated neonatal rat nodose ganglion (NG) neurones. 2 Of the four EP receptor agonists ranging from 0.01 to 10  μ M , the EP 2 receptor agonist (ONO‐AE1‐259, 0.1–10  μ M ) and the EP 4 receptor agonist (ONO‐AE1‐329, 1  μ M ) significantly increased peak I NaR . The responses were associated with a hyperpolarizing shift in the activation curve. 3 Neither the EP 1 receptor agonist ONO‐DI‐004 nor the EP 3 receptor agonist ONO‐AE‐248 significantly modified the properties of I NaR . 4 In PGE 2 applications ranging from 0.01 to 10  μ M , 1  μ M PGE 2 produced a maximal increase in the peak I NaR amplitude. The PGE 2 (1  μ M )‐induced increase in the GV 1/2 baseline (% change in G at baseline V 1/2 ) was significantly attenuated by either intracellular application of the PKA inhibitor PKI or extracellular application of the protein kinase C inhibitor staurosporine (1  μ M ). However, the slope factor k was not significantly altered by PGE 2 applications at 0.01–10  μ M . In addition, the hyperpolarizing shift of V 1/2 by PGE 2 was not significantly altered by either PKI or staurosporine. 5 In other series of experiments, reverse transcription–polymerase chain reaction (RT–PCR) of mRNA from nodose ganglia indicated that all four EP receptors were present. 6 The NG contained many neuronal cell bodies (diameter <30  μ m) with intense or moderate EP 2 , EP 3 , and EP 4 receptor‐immunoreactivities. 7 These results suggest that the PGE 2 ‐induced modification of I NaR is mainly mediated by activation of both EP 2 and EP 4 receptors.British Journal of Pharmacology (2005) 145 , 503–513. doi: 10.1038/sj.bjp.0706212