Failure of repeated electroconvulsive shock treatment on 5-HT4-receptor-mediated depolarization due to protein kinase A system in young rat hippocampal CA1 neurons.
We previously demonstrated that repeated electroconvulsive shock (ECS) treatment enhanced serotonin (5-HT)(1A)- and 5-HT(3)-receptor-mediated responses in hippocampal CA1 pyramidal neurons. The electrophysiological studies were performed to elucidate the effects of ECS treatment on depolarization, which was an additional response induced by 5-HT, and the second messenger system involved in this depolarization of hippocampal CA1 neurons. Both application of 5-HT (100 microM) induced depolarization of the membrane potential in the presence of 5-HT(1A)-receptor antagonists. This depolarization was mimicked by 5-HT(4)-receptor agonists, RS 67506 (1-30 microM) and RS 67333 (0.1-30 microM), in a concentration-dependent manner. 5-HT- and RS 67333-induced depolarization was attenuated by concomitant application of RS 39604, a 5-HT(4)-receptor antagonist. H-89, a protein kinase A (PKA) inhibitor, inhibited 5-HT-, RS 67506-, and RS 67333-induced depolarizations, while forskolin (10 microM), an activator of adenylate cyclase, induced depolarization. Furthermore, RS 67333-induced depolarization was not significantly different between hippocampal slices prepared from rats administered ECS once a day for 14 days and those from sham-treated rats. These findings suggest that 5-HT(4)-receptor-mediated depolarization is caused via the cAMP-PKA system. In addition, repeated ECS-treatment did not modify 5-HT(4)-receptor functions in contrast to 5-HT(1A)- and 5-HT(3)-receptor functions.
Department of Pharmacotherapy, Graduate School of Biomedical Sciences, Hiroshima University, Kasumi, Minami, Hiroshima 734-8551, Japan. ishihara.@ps.hirokoku-u.ac.jp
Kumatoshi
K
Ishihara
Masashi
M
Sasa
D000814:Aniline Compounds / Q000494:pharmacology; D000818:Animals; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D004597:Electroshock; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D009474:Neurons / Q000502:physiology*; D010879:Piperazines / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011407:Propane / Q000031:analogs & derivatives* / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D044422:Receptors, Serotonin, 5-HT4 / Q000502:physiology*; D015290:Second Messenger Systems / Q000502:physiology; D058828:Serotonin 5-HT4 Receptor Agonists; D058832:Serotonin 5-HT4 Receptor Antagonists; D013449:Sulfonamides / Q000494:pharmacology
D000814:Aniline Compounds; D010879:Piperazines; D010880:Piperidines; D011725:Pyridines; C475107:RS 39604; D058828:Serotonin 5-HT4 Receptor Agonists; D058832:Serotonin 5-HT4 Receptor Antagonists; D013449:Sulfonamides; D044422:Receptors, Serotonin, 5-HT4; C107826:RS 67333; C107556:RS 67506; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide; D017868:Cyclic AMP-Dependent Protein Kinases; D011407:Propane