Dasgupta Jaydip, Elliott Ruth A, Doshani Angie, Tincello Douglas G
University of Leicester, Prolapse and Incontinence Group, Reproductive Sciences Section, Department of Cancer Studies and Molecular Medicine, Robert Kilpatrick Clinical Sciences Building, Leicester Royal Infirmary, Leicester, LE2 7LX, UK.
Toxicol Appl Pharmacol. 2006 Dec 1;217(2):216-24. doi: 10.1016/j.taap.2006.09.004. Epub 2006 Sep 12.
Consumption of carbonated soft drinks has been shown to be independently associated with the development of overactive bladder symptoms (OR 1.62, 95% CI 1.18, 2.22) [Dallosso, H.M., McGrother, C.W., Matthews, R.J., Donaldson, M.M.K., 2003. The association of diet and other lifestyle factors with overactive bladder and stress incontinence: a longitudinal study in women. BJU Int. 92, 69-77]. We evaluated the effects of three artificial sweeteners, acesulfame K, aspartame and sodium saccharin, on the contractile response of isolated rat detrusor muscle strips.
Strips of detrusor muscle were placed in an organ bath and stimulated with electrical field stimulation (EFS) in the absence and presence of atropine, and with alpha,beta methylene ATP, potassium, calcium and carbachol.
Sweeteners 10(-7) M to 10(-2) M enhanced the contractile response to 10 Hz EFS compared to control (p<0.01). The atropine-resistant response to EFS was marginally increased by acesulfame K 10(-6) M, aspartame 10(-7) M and sodium saccharin 10(-7) M. Acesulfame K 10(-6) M increased the maximum contractile response to alpha,beta methylene ATP by 35% (+/-9.6%) (p<0.05) and to KCl by 12% (+/-3.1%) (p<0.01). Sodium saccharin also increased the response to KCl by 37% (+/-15.2%) (p<0.05). These sweeteners shifted the calcium concentration-response curves to the left. Acesulfame K 10(-6) M increased the log EC(50) from -2.79 (+/-0.037) to -3.03 (+/-0.048, p<0.01) and sodium saccharin 10(-7) M from -2.74 (+/-0.03) to 2.86 (+/-0.031, p<0.05). The sweeteners had no significant effect on the contractile response to carbachol but they did increase the amplitude of spontaneous bladder contractions.
These results suggest that low concentrations of artificial sweeteners enhanced detrusor muscle contraction via modulation of L-type Ca(+2) channels.
已表明饮用碳酸软饮料与膀胱过度活动症症状的发生独立相关（比值比1.62，95%置信区间1.18，2.22）[达洛索，H.M.，麦格罗瑟，C.W.，马修斯，R.J.，唐纳森，M.M.K.，2003年。饮食及其他生活方式因素与膀胱过度活动症和压力性尿失禁的关联：一项针对女性的纵向研究。《英国泌尿学杂志》92，69 - 77]。我们评估了三种人工甜味剂——安赛蜜、阿斯巴甜和糖精钠对离体大鼠逼尿肌条收缩反应的影响。
将逼尿肌条置于器官浴槽中，在无阿托品和有阿托品的情况下，分别用电场刺激（EFS）以及用α,β - 亚甲基ATP、钾、钙和卡巴胆碱进行刺激。
与对照组相比，浓度为10⁻⁷M至10⁻²M的甜味剂增强了对10Hz EFS的收缩反应（p<0.01）。10⁻⁶M的安赛蜜、10⁻⁷M的阿斯巴甜和10⁻⁷M的糖精钠使对EFS的阿托品抵抗反应略有增加。10⁻⁶M的安赛蜜使对α,β - 亚甲基ATP的最大收缩反应增加35%（±9.6%）（p<0.05），对氯化钾的最大收缩反应增加12%（±3.1%）（p<0.01）。糖精钠也使对氯化钾的反应增加37%（±15.2%）（p<0.05）。这些甜味剂使钙浓度 - 反应曲线向左移动。10⁻⁶M的安赛蜜使对数半数有效浓度（log EC₅₀）从 - 2.79（±0.037）变为 - 3.03（±0.048，p<0.01），10⁻⁷M的糖精钠使对数半数有效浓度从 - 2.74（±0.03）变为 - 2.86（±0.031，p<0.05）。这些甜味剂对卡巴胆碱的收缩反应无显著影响，但它们确实增加了膀胱自发收缩的幅度。
这些结果表明，低浓度的人工甜味剂通过调节L型钙通道增强了逼尿肌收缩。
