Neurotoxic study of H2 antagonists using Xenopus oocytes injected with mouse-brain mRNA
| Autor: | Yasufumi Sawada, Koujirou Yamamoto, Tatsuji Iga, Keiji Yanagisawa, Atsushi Asanuma, Junichi Kawakami, Masafumi Shimokawa |
|---|---|
| Rok vydání: | 1997 |
| Předmět: |
Male
medicine.medical_specialty Kainic acid Patch-Clamp Techniques Microinjections medicine.medical_treatment Xenopus Neurotoxins Pharmaceutical Science Pharmacology Biology H2 antagonist chemistry.chemical_compound Mice Internal medicine Convulsion medicine Animals Quisqualic acid RNA Messenger Cimetidine Brain Chemistry General Medicine Glutamic acid Endocrinology chemistry Histamine H2 Antagonists Convulsant Oocytes NMDA receptor medicine.symptom medicine.drug |
| Zdroj: | Biologicalpharmaceutical bulletin. 20(9) |
| ISSN: | 0918-6158 |
| Popis: | To clarify the dominant mechanism for the convulsant activity of H 2 antagonists, the effects of an H 2 antagonist, cimetidine, on membrane currents induced by various agonists were investigated. In Xenopus oocytes injected with mouse-brain mRNA, acetylcholine (ACh), serotonin (5-HT), γ-aminobutyric acid (GABA), glycine (Gly), glutamic acid (Glu), kainic acid (KA), quisqualic acid (QA) and N-methyl-D-aspartic acid (NMDA)-induced current responses were recorded under a voltage-clamp condition. Cimetidine inhibited GABA-induced currents in a concentration-dependent manner; however, the current responses induced by the other agonists were not modified. The IC 50 of various H 2 antagonists, famotidine, nizatidine, cimetidine and ranitidine, for GABA (10 μM)-induced current response were 66, 260, 450 and 980 μM, respectively. However, these values of cimetidine and ranitidine were 40-400 times higher than the reported brain and cerebrospinal fluid (CSF) concentration of H 2 antagonists at the occurrence of a clonic convulsion in vivo. In conclusion, we observed an inhibitory effect of H 2 antagonists on the GABA response; however, this inhibition of GABA-mediated neurotransmission may not be the dominant mechanism for H 2 antagonist-induced clonic convulsion in vivo. |
| Databáze: | OpenAIRE |
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