Prostaglandin E2-induced modification of tetrodotoxin-resistant Na+ currents involves activation of both EP2 and EP4 receptors in neonatal rat nodose ganglion neurones.
1 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 (I(NaR)) in acutely isolated neonatal rat nodose ganglion (NG) neurones. 2 Of the four EP receptor agonists ranging from 0.01 to 10 muM, the EP2 receptor agonist (ONO-AE1-259, 0.1-10 microM) and the EP4 receptor agonist (ONO-AE1-329, 1 microM) significantly increased peak I(NaR). The responses were associated with a hyperpolarizing shift in the activation curve. 3 Neither the EP1 receptor agonist ONO-DI-004 nor the EP3 receptor agonist ONO-AE-248 significantly modified the properties of I(NaR). 4 In PGE2 applications ranging from 0.01 to 10 microM, 1 microM PGE2 produced a maximal increase in the peak I(NaR) amplitude. The PGE2 (1 microM)-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 microM). However, the slope factor k was not significantly altered by PGE2 applications at 0.01-10 microM. In addition, the hyperpolarizing shift of V(1/2) by PGE2 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 microm) with intense or moderate EP2, EP3, and EP4 receptor-immunoreactivities. 7 These results suggest that the PGE2-induced modification of I(NaR) is mainly mediated by activation of both EP2 and EP4 receptors.
Matsumoto
Shigeji
S
Department of Physiology, Nippon Dental University, School of Dentistry at Tokyo, 1-9-20 Fujimi, Chiyoda-ku, Tokyo 102-8159, Japan.
Ikeda
Mizuho
M
Yoshida
Shinki
S
Tanimoto
Takeshi
T
Takeda
Mamoru
M
Nasu
Masanori
M
D000527:Alprostadil / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D015232:Dinoprostone / Q000031:analogs & derivatives / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005459:Fluorides / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D007150:Immunohistochemistry; D008564:Membrane Potentials / Q000187:drug effects; D008738:Methyl Ethers / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D009620:Nodose Ganglion / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018078:Receptors, Prostaglandin E / Q000819:agonists / Q000235:genetics / Q000502:physiology*; D058306:Receptors, Prostaglandin E, EP1 Subtype; D058307:Receptors, Prostaglandin E, EP2 Subtype; D058308:Receptors, Prostaglandin E, EP3 Subtype; D058309:Receptors, Prostaglandin E, EP4 Subtype; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015222:Sodium Channels / Q000502:physiology*; D019311:Staurosporine / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology*; D013997:Time Factors
C499423:9-deoxy-9-chloro-15-deoxy-16-hydroxy-17,17-trimethylene-19,20-didehydroprostaglandin E2; D004791:Enzyme Inhibitors; D008738:Methyl Ethers; C121546:ONO AE 248; C461399:ONO-AE1-329; C500045:ONO-DI-004; D047428:Protein Kinase Inhibitors; C545637:Ptger1 protein, rat; C545646:Ptger2 protein, rat; C545649:Ptger3 protein, rat; C545652:Ptger4 protein, rat; D012333:RNA, Messenger; D018078:Receptors, Prostaglandin E; D058306:Receptors, Prostaglandin E, EP1 Subtype; D058307:Receptors, Prostaglandin E, EP2 Subtype; D058308:Receptors, Prostaglandin E, EP3 Subtype; D058309:Receptors, Prostaglandin E, EP4 Subtype; D015222:Sodium Channels; D013779:Tetrodotoxin; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D000527:Alprostadil; D019311:Staurosporine; D015232:Dinoprostone; D005459:Fluorides