Serotonin 2C Receptor (5-HT2CR) mRNA Editing-Induced Down-Regulation of 5-HT2CR Function in Xenopus Oocytes: the Significance of Site C Editing
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-e...
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2010-01-01T00:00:00Z.
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|---|---|---|---|
| 001 | doaj_b6d82273d2db4ad989b2c322b36cd8f4 | ||
| 042 | |a dc | ||
| 100 | 1 | 0 | |a Michihisa Tohda |e author |
| 700 | 1 | 0 | |a Pham T.N. Hang |e author |
| 700 | 1 | 0 | |a Naofumi Kobayashi |e author |
| 700 | 1 | 0 | |a Kinzo Matsumoto |e author |
| 245 | 0 | 0 | |a Serotonin 2C Receptor (5-HT2CR) mRNA Editing-Induced Down-Regulation of 5-HT2CR Function in Xenopus Oocytes: the Significance of Site C Editing |
| 260 | |b Elsevier, |c 2010-01-01T00:00:00Z. | ||
| 500 | |a 1347-8613 | ||
| 500 | |a 10.1254/jphs.10094FP | ||
| 520 | |a 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. Keywords:: RNA editing, serotonin 2C receptor subtype, phospholipase C, Xenopus oocyte | ||
| 546 | |a EN | ||
| 690 | |a Therapeutics. Pharmacology | ||
| 690 | |a RM1-950 | ||
| 655 | 7 | |a article |2 local | |
| 786 | 0 | |n Journal of Pharmacological Sciences, Vol 113, Iss 4, Pp 362-367 (2010) | |
| 787 | 0 | |n http://www.sciencedirect.com/science/article/pii/S134786131930903X | |
| 787 | 0 | |n https://doaj.org/toc/1347-8613 | |
| 856 | 4 | 1 | |u https://doaj.org/article/b6d82273d2db4ad989b2c322b36cd8f4 |z Connect to this object online. |