Alteration of serotonin 2C receptor expression in the aorta and the pulmonary artery in rats exposed to hypoxia.
In the present study we reported the expression of the 5-HT2C receptor (5-HT2C-R) in the aorta and the pulmonary artery in rats exposed to hypoxia, and examined its role in vascular smooth muscle cells. Immunochemistry, quantitative RT-PCR, and western blot were used to examine 5-HT2C-R expression. Small interfering RNA (siRNA) was used to explore the role of 5-HT2C-R in vascular smooth muscle cells proliferation and contraction induced by 5-HT.5-HT2C-R immunoreactivity was confined predominantly to the plasma membrane in the rat aortic smooth muscle cells (ASMCs) and the pulmonary arterial smooth muscle cells (PASMCs). 5-HT2C-R mRNA expression in the aorta of hypoxic pulmonary hypertension (HPH) rats was more than that in the pulmonary artery. Hypoxia-induced 5-HT2C-R protein expression in the aorta was less than that in the pulmonary artery, indicating that 5-HT2C-R might mediate different responses of the aorta and the pulmonary artery to 5-HT in HPH. We also demonstrated that RNA editing may not be involved in the different expression levels of 5-HT2C-R in the aorta and the pulmonary artery. The higher expression of 5-HT2C-R in the pulmonary artery versus the aorta of HPH rats was partly due to the increased protein stability. siRNA was used to knock down the expression of 5-HT2C-R. 5-HT2C-R-specific siRNA reduced the proliferation and contraction of vascular smooth muscle cells induced by 5-HT. In conclusion, the different expression patterns of 5-HT2C-R protein in the aorta and the pulmonary artery suggest that this 5-HT receptor may be involved, at least partly, in modulating different responses of systemic vessels and pulmonary vasculature to 5-HT in HPH.
Zhang
Bo
B
Department of Pathophysiology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, Shaanxi, People's Republic of China.
Liu
Yi
Y
Luo
Ying
Y
Niu
Wen
W
Li
Zhi-Chao
ZC
D000818:Animals; D001011:Aorta / Q000378:metabolism*; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D000860:Hypoxia / Q000378:metabolism* / Q000473:pathology; D008297:Male; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000378:metabolism; D011651:Pulmonary Artery / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D044405:Receptor, Serotonin, 5-HT2C / Q000235:genetics / Q000378:metabolism*
D012333:RNA, Messenger; D044405:Receptor, Serotonin, 5-HT2C