title: Upregulation of 5-hydroxytryptamine receptor signaling in coronary arteries after organ culture.
abstract: BACKGROUND
  5-Hydroxytryptamine (5-HT) is a powerful constrictor of coronary arteries and is considered to be involved in the pathophysiological mechanisms of coronary-artery spasm. However, the mechanism of enhancement of coronary-artery constriction to 5-HT during the development of coronary artery disease remains to be elucidated. Organ culture of intact blood-vessel segments has been suggested as a model for the phenotypic changes of smooth muscle cells in cardiovascular disease.
  
  
  RESULTS
  We wished to characterize 5-HT receptor-induced vasoconstriction and quantify expression of 5-HT receptor signaling in cultured rat coronary arteries. Cumulative application of 5-HT produced a concentration-dependent vasoconstriction in fresh and 24 h-cultured rat coronary arteries without endothelia. 5-HT induced greater constriction in cultured coronary arteries than in fresh coronary arteries. U46619- and CaCl2-induced constriction in the two groups was comparable. 5-HT stimulates the 5-HT2A receptor and cascade of phospholipase C to induce coronary vasoconstriction. Calcium influx through L-type calcium channels and non-L-type calcium channels contributed to the coronary-artery constrictions induced by 5-HT. The contractions mediated by non-L-type calcium channels were significantly enhanced in cultured coronary arteries compared with fresh coronary arteries. The vasoconstriction induced by thapsigargin was also augmented in cultured coronary arteries. The decrease in Orai1 expression significantly inhibited 5-HT-evoked entry of Ca2+ in coronary artery cells. Expression of the 5-HT2A receptor, Orai1 and STIM1 were augmented in cultured coronary arteries compared with fresh coronary arteries.
  
  
  CONCLUSIONS
  An increased contraction in response to 5-HT was mediated by the upregulation of 5-HT2A receptors and downstream signaling in cultured coronary arteries.
authors.affiliation: Medical Research Center of Guangdong General Hospital, Guangzhou, P.R. China; Guangdong Provincial Cardiovascular Institute, Guangdong Academy of Medical Sciences, Guangzhou, P.R. China.
authors.forename: Chun-Yu
authors.initials: CY
authors.lastname: Deng
authors.affiliation: Medical Research Center of Guangdong General Hospital, Guangzhou, P.R. China; Guangdong Provincial Cardiovascular Institute, Guangdong Academy of Medical Sciences, Guangzhou, P.R. China.
authors.forename: Hui
authors.initials: H
authors.lastname: Yang
authors.affiliation: Medical Research Center of Guangdong General Hospital, Guangzhou, P.R. China; Guangdong Provincial Cardiovascular Institute, Guangdong Academy of Medical Sciences, Guangzhou, P.R. China.
authors.forename: Su-Juan
authors.initials: SJ
authors.lastname: Kuang
authors.affiliation: Medical Research Center of Guangdong General Hospital, Guangzhou, P.R. China; Guangdong Provincial Cardiovascular Institute, Guangdong Academy of Medical Sciences, Guangzhou, P.R. China.
authors.forename: Fang
authors.initials: F
authors.lastname: Rao
authors.affiliation: Medical Research Center of Guangdong General Hospital, Guangzhou, P.R. China; Guangdong Provincial Cardiovascular Institute, Guangdong Academy of Medical Sciences, Guangzhou, P.R. China.
authors.forename: Yu-Mei
authors.initials: YM
authors.lastname: Xue
authors.affiliation: Medical Research Center of Guangdong General Hospital, Guangzhou, P.R. China; Guangdong Provincial Cardiovascular Institute, Guangdong Academy of Medical Sciences, Guangzhou, P.R. China.
authors.forename: Zhi-Ling
authors.initials: ZL
authors.lastname: Zhou
authors.affiliation: Medical Research Center of Guangdong General Hospital, Guangzhou, P.R. China; Guangdong Provincial Cardiovascular Institute, Guangdong Academy of Medical Sciences, Guangzhou, P.R. China.
authors.forename: Xiao-Ying
authors.initials: XY
authors.lastname: Liu
authors.affiliation: Medical Research Center of Guangdong General Hospital, Guangzhou, P.R. China; Guangdong Provincial Cardiovascular Institute, Guangdong Academy of Medical Sciences, Guangzhou, P.R. China.
authors.forename: Zhi-Xin
authors.initials: ZX
authors.lastname: Shan
authors.affiliation: Medical Research Center of Guangdong General Hospital, Guangzhou, P.R. China; Guangdong Provincial Cardiovascular Institute, Guangdong Academy of Medical Sciences, Guangzhou, P.R. China.
authors.forename: Xiao-Hong
authors.initials: XH
authors.lastname: Li
authors.affiliation: Medical Research Center of Guangdong General Hospital, Guangzhou, P.R. China; Guangdong Provincial Cardiovascular Institute, Guangdong Academy of Medical Sciences, Guangzhou, P.R. China.
authors.forename: Qiu-Xiong
authors.initials: QX
authors.lastname: Lin
authors.affiliation: Medical Research Center of Guangdong General Hospital, Guangzhou, P.R. China; Guangdong Provincial Cardiovascular Institute, Guangdong Academy of Medical Sciences, Guangzhou, P.R. China.
authors.forename: Shu-Lin
authors.initials: SL
authors.lastname: Wu
authors.affiliation: Medical Research Center of Guangdong General Hospital, Guangzhou, P.R. China; Guangdong Provincial Cardiovascular Institute, Guangdong Academy of Medical Sciences, Guangzhou, P.R. China.
authors.forename: Xi-Yong
authors.initials: XY
authors.lastname: Yu
mesh_terms: D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism; D020746:Calcium Channels, L-Type / Q000235:genetics / Q000378:metabolism; D003331:Coronary Vessels / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism; D000071740:ORAI1 Protein; D009924:Organ Culture Techniques / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D044402:Receptor, Serotonin, 5-HT2A / Q000235:genetics* / Q000378:metabolism; D012701:Serotonin / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics*; D000071737:Stromal Interaction Molecule 1; D019284:Thapsigargin / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics*; D014661:Vasoconstriction / Q000187:drug effects / Q000235:genetics
chemical_list: D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D008562:Membrane Glycoproteins; D000071740:ORAI1 Protein; C532493:Orai1 protein, rat; D044402:Receptor, Serotonin, 5-HT2A; C518857:Stim1 protein, rat; D000071737:Stromal Interaction Molecule 1; D012701:Serotonin; D019284:Thapsigargin; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D002118:Calcium