Prostaglandin E2-induced modification of tetrodotoxin-resistant Na+currents involves activation of both EP2and EP4receptors in neonatal rat nodose ganglion neurones

Autor: Shinki Yoshida, Mamoru Takeda, Shigeji Matsumoto, Mizuho Ikeda, Masanori Nasu, Takeshi Tanimoto
Rok vydání: 2005
Předmět:
Zdroj: British Journal of Pharmacology. 145:503-513
ISSN: 0007-1188
Popis: The aim of the present study was to investigate which EP receptor subtypes (EP1–EP4) act predominantly on the modification of the tetrodotoxin-resistant Na+ current (INaR) in acutely isolated neonatal rat nodose ganglion (NG) neurones. Of the four EP receptor agonists ranging from 0.01 to 10 μM, the EP2 receptor agonist (ONO-AE1-259, 0.1–10 μM) and the EP4 receptor agonist (ONO-AE1-329, 1 μM) significantly increased peak INaR. The responses were associated with a hyperpolarizing shift in the activation curve. Neither the EP1 receptor agonist ONO-DI-004 nor the EP3 receptor agonist ONO-AE-248 significantly modified the properties of INaR. In PGE2 applications ranging from 0.01 to 10 μM, 1 μM PGE2 produced a maximal increase in the peak INaR amplitude. The PGE2 (1 μM)-induced increase in the GV1/2 baseline (% change in G at baseline V1/2) was significantly attenuated by either intracellular application of the PKA inhibitor PKI or extracellular application of the protein kinase C inhibitor staurosporine (1 μM). However, the slope factor k was not significantly altered by PGE2 applications at 0.01–10 μM. In addition, the hyperpolarizing shift of V1/2 by PGE2 was not significantly altered by either PKI or staurosporine. 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. The NG contained many neuronal cell bodies (diameter
Databáze: OpenAIRE