摘要
研究发现在人类气道平滑肌上存在苦味受体(bitter taste receptors,TAS2Rs),可感知苦味物质,引起局部Ca2+增加,却使肺部支气管高效扩张,从而有效缓解哮喘、慢性阻塞性肺疾病(chronic obstructive pulmonary diseases,COPD)等患者的气道痉挛,降低气道阻力。临床上对于哮喘的治疗仍面临很大难题,肺部TAS2R或许成为一种新的治疗靶点。但其引起气道舒张的确切机制尚不清楚,文中对TAS2R的结构、信号转导及刺激肺部TAS2R引起气道扩张的分子机制进行综述。
Bitter taste receptors have recently been identified on human's airway smooth muscle( ASM),which can perceive bitter substances and evoke increased intracellular calcium( [Ca2 +]i) in airway smooth muscle. They can cause lung bronchial efficient expansion,and thus effectively alleviate airway spasm and airway resistance in asthma,chronic obstructive pulmonary disease. Clinically,the treatment of asthma remains challengeable,lung TAS2 R may be a new treatment target. However,its mechanism is unclear,this paper describes the structure of bitter taste receptors,signal transduction and mechanisms of airway dilatation when bitter taste receptors were activated.
引文
[1]李黎,刘文雅,侯中华.急支平喘软胶囊的镇咳平喘化痰药效研究[J].医学研究生学报,2014,27(11):1194-1196.
[2]戴伟,吴洁,辛晓峰.精氨酸酶在气道炎症和气道重塑中的作用[J].医学研究生学报,2015,28(2):221-224.
[3]石亚琴,施毅,吴婷,等.哮喘合并侵袭性肺曲霉病[J].医学研究生学报,2015,27(8):866-870.
[4]Deshpande DA,Wang WC,Mc Ilmoyle EL,et al.Bitter taste receptors on airway smooth muscle bronchodilate by localized calcium signaling and reverse obstruction[J].Nat Med,2010,16(11):1299-1304.
[5]Elliott RA,Kapoor S,Tincello DG.Expression and distribution of the sweet taste receptor isoforms T1R2 and T1R3 in human and rat bladders[J].J Urol,2011,186(6):2455-2462.
[6]Doggrell SA.Bitter taste receptors as a target for bronchodilation[J].Expert Opin Ther Targets,2011,15(7):899-902.
[7]Zhang CH,Chen C,Lifshitz LM,et al.Activation of BK channels may not be required for bitter tastant-induced bronchodilation[J].Nat Med,2012,18(5):648-650.
[8]胡晓燕.氯喹对哮喘小鼠的气道炎症及气道高反应性的作用及机制[D].重庆:重庆医科大学,2014,25-38.
[9]Grassin-Delyle S,Naline E,Devillier P.Taste receptors in asthma[J].Curr Opin Allergy Clin Immunol,2015,15(1):63-69.
[10]Robinett KS,Deshpande DA,Malone MM,Liggett SB.Agonistpromoted homologous desensitization of human airway smooth muscle bitter taste receptors[J].Am J Respir Cell Mol Biol,2011,45(5):1069-1074.
[11]An SS,Wang WC,Koziol-White CJ,et al.TAS2R activation promotes airway smooth muscle relaxation despite beta(2)-adrenergic receptor tachyphylaxis[J].Am J Physiol Lung Cell Mol Physiol.2012.303(4):L304-L311.
[12]Orsmark-Pietras C,James A,Konradsen JR,et al.Transcriptome analysis reveals upregulation of bitter taste receptors in severe asthmatics[J].Eur Respir J,2013,42(1):65-78.
[13]Roland WS,Vincken JP,Gouka RJ,et al.Soy isoflavones and other isoflavonoids activate the human bitter taste receptors h TAS2R14 and h TAS2R39[J].J Agric Food Chem,2011,59(21):11764-11771.
[14]Aoki M,Takao T,Takao K,et al.Lower expressions of the human bitter taste receptor TAS2R in smokers:reverse transcriptase-polymerase chain reaction analysis[J].Tob Induc Dis,2014,12(1):12.
[15]Sekine H,Takao K,Yoshinaga K,et al.Effects of zinc deficiency and supplementation on gene expression of bitter taste receptors(TAS2Rs)on the tongue in rats[J].Laryngoscope,2012,122(11):2411-2417.
[16]Mennella JA,Pepino MY,Duke FF,et al.Age modifies the genotype-phenotype relationship for the bitter receptor TAS2R38[J].BMC Genet,2010,11:60.
[17]方丽萍,赵明,张鹏鹏,等.难治性哮喘患者血清肿瘤坏死因子-α的表达及其与肺功能和气道炎症的关系[J].医学研究生学报,2014,27(1):55-57.
[18]Lee RJ,Cohen NA.Bitter and sweet taste receptors in the respiratory epithelium in health and disease[J].J Mol Med(Berl),2014,92(12):1235-1244.
[19]Lee RJ,Cohen NA.Taste receptors in innate immunity[J].Cell Mol Life Sci,2015,72(2):217-236.
[20]Lee RJ,Cohen NA.Role of the bitter taste receptor T2R38 in upper respiratory infection and chronic rhinosinusitis[J].Curr Opin Allergy Clin Immunol,2015,15(1):14-20.
[21]吴海兰,辛晓峰.上皮间充质转化与慢性阻塞性肺疾病的气道重塑[J].医学研究生学报,2015,28(9):1004-1008.
[22]Krasteva G,Canning BJ,Hartmann P,et al.Cholinergic chemosensory cells in the trachea regulate breathing[J].Proc Natl Acad Sci USA,2011,108(23):9478-9483.
[23]Shah AS,Ben-Shahar Y,Moninger TO,et al.Motile cilia of human airway epithelia are chemosensory[J].Science,2009,325(5944):1131-1134.
[24]Tizzano M,Gulbransen BD,Vandenbeuch A,et al.Nasal chemosensory cells use bitter taste signaling to detect irritants and bacterial signals[J].Proc Natl Acad Sci USA,2010,107(7):3210-3215.
[25]Saunders CJ,Christensen M,Finger TE,et al.Cholinergic neurotransmission links solitary chemosensory cells to nasal inflammation[J].Proc Natl Acad Sci USA,2014,111(16):6075-6080.
[26]Levit A,Nowak S,Peters M,et al.The bitter pill:clinical drugs that activate the human bitter taste receptor TAS2R14[J].FASEB J,2014,28(3):1181-1197.
