5-羟色胺(5-HT)可以增强人的输尿管收缩。然而,介导受体尚未明确。该研究试图使用几种选择性拮抗剂和激动剂进一步表征介导受体。从92例接受膀胱切除术的患者中获得了人远端输尿管。使用RT-qPCR实验检查5-HT受体的mRNA表达水平。输尿管条的阶段性收缩,无论是自发的还是神经激肽诱发的,被记录在器官浴中。在13个5-HT受体中,5-HT2A和5-HT2C受体显示最高的mRNA表达水平。5-HT(10-7-10-4M)以浓度依赖性方式增加了阶段性收缩的频率和基线张力。然而,观察到脱敏效果。5-HT2C受体选择性拮抗剂,SB242084(10,30,100nM),将5-HT浓度-反应曲线(频率和基线张力)向右移动,pA2值分别为8.05和7.75。5-HT2C受体选择性激动剂,vabicaserin,5-HT的Emax为35%时,收缩频率增加。5-HT2A受体选择性拮抗剂,volinanserin(1,10,100nM),仅在pA2为8.18时降低基线张力。5-HT1A的选择性拮抗剂,1B,1D,2B,3、4、5、6和7没有拮抗作用。电压门控钠通道的阻断,α1-肾上腺素能受体,肾上腺素能神经传递,和神经激肽-2受体使用河豚毒素,坦索罗辛,胍乙啶,和Men10376,分别,并使用辣椒素(100μM)对感觉传入进行脱敏,显著降低5-HT效应。我们得出的结论是,5-HT主要通过激活5-HT2C和5-HT2A受体来增强输尿管阶段性收缩。交感神经和感觉传入部分促成了5-HT效应。5-HT2C和5-HT2A受体可能是输尿管结石排出的有希望的靶标。
5-Hydroxytryptamine (5-HT) can enhance human ureteral contractions. However, the mediating receptors have not been clarified. This study sought to further characterize the mediating receptors using several selective antagonists and agonists. Human distal ureters were obtained from 96 patients undergoing cystectomy. The mRNA expression levels of 5-HT receptors were examined using RT-qPCR experiments. The phasic contractions of ureter strips, either spontaneous or evoked with neurokinin, were recorded in an organ bath. Among the 13 5-HT receptors, 5-HT2A and 5-HT2C receptors showed the highest mRNA expression levels. 5-HT (10-7-10-4 M) increased the frequency and baseline tension of phasic contractions in a concentration-dependent manner. However, a desensitization effect was observed. The 5-HT2C receptor selective antagonist, SB242084 (10,30,100 nM), shifted the 5-HT concentration-response curves (frequency and baseline tension) rightward with a pA2 value of 8.05 and 7.75, respectively. 5-HT2C receptor selective agonist, vabicaserin, increased contraction frequency with an Emax of 35% of 5-HT. 5-HT2A receptor selective antagonist, volinanserin (1,10,100 nM), only reduced baseline tension with a pA2 of 8.18. The selective antagonists of 5-HT1A, 1B, 1D, 2B, 3, 4, 5, 6, and 7 had no antagonism. Blockade of voltage-gated sodium channels, α1-adrenergic receptors, adrenergic neurotransmission, and neurokinin-2 receptors using tetrodotoxin, tamsulosin, guanethidine, and Men10376, respectively, and desensitization of sensory afferents using capsaicin (100 μM), significantly reduced 5-HT effects. We conclude that 5-HT enhanced ureteral phasic contractions mainly by activating 5-HT2C and 5-HT2A receptors. Sympathetic nerve and sensory afferents partly contributed to 5-HT effects. 5-HT2C and 5-HT2A receptors could be promising targets for ureteral stone expulsion.