Abstract
Artificial sweeteners augment bladder contraction. We hypothesized that artificial sweeteners activate sweet taste receptors in the bladder. Thus, we investigated the expression of sweet taste receptors in human and rat bladders. Sections of human and rat bladders were cut from paraffin blocks and stained by immunohistochemistry for the expression of T1R2/3 sweet taste receptors. Bladder homogenates were subjected to sodium dodecyl sulfate-polyacrylamide electrophoresis, followed by immunoblotting for T1R2/3 receptor expression. Rat bladder strips with and without urothelium were suspended in organ baths. The contractile response to 10 Hz electrical field stimulation was determined in the absence and presence of saccharin (Sigma-Aldrich®) (10(-8) to 10(-3) M). Responses to KCl in the absence and presence of saccharin, and saccharin plus zinc were also determined. T1R2/3 sweet taste receptors were expressed in human and rat bladder urothelium. Immunostaining was evident in the plasma membrane of the 3 urothelial cell types, particularly umbrella cells. Immunoblotting revealed bands at expected molecular weights in human and rat bladder homogenates. Saccharin augmented rat bladder smooth muscle contraction due to electrical field stimulation only when urothelium was present in the bladder strip. Zinc blocked the enhancing effect of saccharin on responses to KCl. T1R2/3 sweet taste receptors are expressed in human and rat bladder urothelium. Activation of these receptors by artificial sweeteners may result in augmented bladder contraction.
Highlights
The International Continence Society definition of overactive bladder (OAB) is urgency with or without urge incontinence, usually with frequency and nocturia[1]
T1R2 and T1R3 sweet taste receptors were expressed in the urothelium of human and rat bladder
Saccharin augmented rat bladder smooth muscle contraction to electrical field stimulation only when the urothelium was present in the bladder strip
Summary
The International Continence Society definition of overactive bladder (OAB) is urgency with or without urge incontinence, usually with frequency and nocturia[1]. A recent prevalence study, conducted in five countries demonstrated OAB prevalence to be 11.8% (10.9% for men and 12.9% for women) increasing with age[2]. OAB has significant socioeconomic burdens and a negative impact on quality of life[3]. The mainstay of therapy is anticholinergic drugs, which are effective but after long term treatment the incidence of adverse effects is high[4]. Newer therapies which enhance the detrusor muscle’s relaxation mechanisms[4] are being evaluated, but for pharmacotherapy of OAB is limited. There are, other influences on bladder function such as diet and lifestyle factors
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