Enhanced transcription of serotonin receptor 2B in dorsal root ganglion from ASIC3 knockout mice

• Main Authors: Chun-Ying Huang, 黃淳瑩
• Other Authors: Wei-hsin Sun
• Format: Others
• Language: zh-TW
• Published: 2005
• Online Access: http://ndltd.ncl.edu.tw/handle/95941386959059245306

碩士 === 國立中央大學 === 生命科學研究所 === 94 === Abstract Tissue acidosis, an important feature of tissue injury or inflammation, is a dominant factor causing pain. Among those acid sensing receptors, acid sensing ion channel 3 (ASIC3) is believed to be the major receptor responsible for acid-induced pain. Surprisingly, ASIC3-deficient mice have displayed a higher sensitivity in pain sensation than wild-type mice. It is likely that other molecules compensate ASIC3-deficiency. Using microarray analysis, previous studies have found that the transcripts of serotonin receptor 2B (5-HT2B) are up-regulated in ASIC3 knockout mice. However, the role of 5-HT2B in pain sensation and its relationship with ASIC3 remain unclear. The objective of this thesis is to explore the function of 5-HT2B in pain and to understand the relationship between 5-HT2B and ASIC3. To achieve this aim, I first confirmed the results of microarray and examined 5-HT2B distribuction. 5-HT2B is expressed in all tested tissues from wild-type and ASIC3 knockout mice. The expression is enhanced two folds in dorsal root ganglion (DRG) from ASIC3 knockout mice. Using in situ hybridization, I have found that the majority of 5-HT2B is expressed in a subset of pain-relevant, small-diameter neurons, and this population increases in ASIC3 knockout DRG. Since serotonin increases ASIC3 transcripts and 5-HT2B transcription is enhanced in a loss of ASIC3 gene, it is possible that serotonin enhances ASIC3 transcription through 5-HT2B. To test this hypothesis, I have cloned ASIC3 promoter to examine the promoter activity in the presence of 5-HT2B. After serotonin stimulation, ASIC3 promoter activity is not enhanced, even though 5-HT2B is activated. The possible reasons will be discussed in the thesis.