PDF(Pubmed)
Abstract：
It is unclear whether bufotenin (= N,N-dimethyl-serotonin = 5-hydroxy-N,N-dimethyl-tryptamine), a hallucinogenic drug, can act on human cardiac serotonin 5-HT4 receptors. Therefore, the aim of the study was to examine the cardiac effects of bufotenin and for comparison tryptamine in transgenic mice that only express the human 5-HT4 receptor in cardiomyocytes (5-HT4-TG), in their wild-type littermates (WT) and in isolated electrically driven (1 Hz) human atrial preparations. In 5-HT4-TG, we found that both bufotenin and tryptamine enhanced the force of contraction in left atrial preparations (pD2 = 6.77 or 5.5, respectively) and the beating rate in spontaneously beating right atrial preparations (pD2 = 7.04 or 5.86, respectively). Bufotenin (1 µM) increased left ventricular force of contraction and beating rate in Langendorff perfused hearts from 5-HT4-TG, whereas it was inactive in hearts from WT animals, as was tryptamine. The positive inotropic and chronotropic effects of bufotenin and tryptamine were potentiated by an inhibitor of monoamine oxidases (50 µM pargyline). Furthermore, bufotenin concentration- (0.1-10 µM) and time-dependently elevated force of contraction in isolated electrically stimulated musculi pectinati from the human atrium and these effects were likewise reversed by tropisetron (10 µM). We found that bufotenin (10 µM) increased the phosphorylation state of phospholamban in the isolated perfused hearts, left and right atrial muscle strips of 5-HT4-TG but not from WT and in isolated human right atrial preparations. In summary, we showed that bufotenin can increase the force of contraction via stimulation of human 5-HT4 receptors transgenic mouse cardiac preparations but notably also in human atrial preparations.
摘要：
目前尚不清楚bufotenin(=N，N-二甲基-5-羟色胺=5-羟基-N，N-二甲基色胺)，一种致幻药物,可以对人心脏5-羟色胺5-HT4受体起作用。因此,这项研究的目的是检查bufotenin的心脏效应，并比较仅在心肌细胞中表达人5-HT4受体（5-HT4-TG）的转基因小鼠中的色胺，在其野生型同窝窝（WT）和分离的电驱动（1Hz）人心房制剂中。在5-HT4-TG中，我们发现，bufotenin和色胺均可增强左心房制剂的收缩力（分别为pD2=6.77或5.5）和自发搏动右心房制剂的搏动率（分别为pD2=7.04或5.86）。Bufotenin（1µM）增加了Langendorff从5-HT4-TG灌注心脏的左心室收缩力和搏动率，而它在WT动物的心脏中不活跃，色胺也是如此。单胺氧化酶抑制剂（50µMpargyline）增强了bufotenin和色胺的正性肌力和变时作用。此外，人心房中孤立的电刺激肌肉中的bufotenin浓度-（0.1-10µM）和时间依赖性的收缩力升高，这些作用同样被托烷司琼（10µM）逆转。我们发现bufotenin（10µM）增加了在分离的灌注心脏中的磷脂的磷酸化状态，5-HT4-TG的左心房肌条和右心房肌条，但不来自WT和分离的人右心房制剂。总之,我们表明，bufotenin可以通过刺激人5-HT4受体转基因小鼠心脏制剂来增加收缩力，尤其是在人心房制剂中。
