Serotonin 2C Receptor (5-HT2CR) mRNA Editing-Induced Down-Regulation of 5-HT2CR Function in Xenopus Oocytes: the Significance of Site C Editing
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- Tohda Michihisa
- Division of Medicinal Pharmacology, Institute of Natural Medicine, University of Toyama, Japan
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- Hang Pham T.N.
- Division of Medicinal Pharmacology, Institute of Natural Medicine, University of Toyama, Japan
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- Kobayashi Naofumi
- Division of Medicinal Pharmacology, Institute of Natural Medicine, University of Toyama, Japan
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- Matsumoto Kinzo
- Division of Medicinal Pharmacology, Institute of Natural Medicine, University of Toyama, Japan
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抄録
Serotonin 2C receptor (5-HT2CR) mRNA receives editing at 5 nucleotide positions (sites A – E) located in the sequence encoding the second intracellular loop of 5-HT2CR. 5-HT2CR mRNA without editing and with editing at sites AB, ABD, ABC, ABCD, and C are translated to 6 isoforms of 5-HT2CR: INI(non-edited), VNI(AB), VNV(ABD), VSI(ABC), VSV(ABCD), and ISI(C), respectively. In this study, we investigated electrophysiologically the ability of these isoforms to couple with the G protein / phospholipase C (PLC) system using Xenopus oocytes injected with edited 5-HT2CR RNAs and muscarinic M1 receptor (M1R) RNA. The efficacy with which 5-HT stimulated each isoform was calculated by comparing 5-HT–induced current with 100 μM acetylcholine–induced M1R current. Stimulation with 5-HT of INI(non-edited), VNI(AB), VNV(ABD), VSI(ABC), VSV(ABCD), and ISI(C) expressed in Xenopus oocytes showed concentration-dependent responses with EC50 values of 8.6, 17.2, 76,5, 22.0, 91.2, and 20.3 nM, respectively. No significant difference in the ability of 5-HT to induce currents among the oocytes expressing these isoforms was detected, but in the oocytes expressing VSI(ABC) or VSV(ABCD), 5-HT had a significantly reduced ability to induce currents. These results suggest that editing at site C together with sites A and B and/or D markedly reduces 5-HT2CR function by generating isoforms with reduced ability to activate PLC.
収録刊行物
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- Journal of Pharmacological Sciences
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Journal of Pharmacological Sciences 113 (4), 362-367, 2010
公益社団法人 日本薬理学会
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詳細情報 詳細情報について
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- CRID
- 1390001205179605504
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- NII論文ID
- 10027746106
- 130000301213
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- NII書誌ID
- AA11806667
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- COI
- 1:CAS:528:DC%2BC3cXhtFegtLvN
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- ISSN
- 13478648
- 13478613
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- NDL書誌ID
- 10790629
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- PubMed
- 20668366
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- 本文言語コード
- en
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- データソース種別
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- JaLC
- NDL
- Crossref
- PubMed
- CiNii Articles
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- 使用不可