Pharmacology of the thromboxane system in detrusor smooth muscle of the human urinary bladder

• Applicant: Professor Dr. Martin Hennenberg
• Subject Area: Reproductive Medicine, Urology
• Term: from 2012 to 2018
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 228188332

Lower urinary tract symptoms (LUTS) may be caused by an overactive bladder (OA), or by benign prostatic obstruction (BPO). LUTS affect considerable parts of the population. Consequences range from a decreased quality of life over depressions to social isolation. An overactive bladder is frequently caused by hyperactivity of the detrusor, i. e. of the smooth muscle in the urinary bladder wall. In detrusor hyperactivity, increased spontaneous, phasic contractions result in urgency with increased micturition frequency, and finally in incontinence. BPO is frequently related to benign prostatic enlargement (BPE), where an increased prostatic smooth muscle tone ("dynamic component") and an increased prostatic volume ("static component") may cause voiding symptoms. According to the important role of smooth muscle tone for micturition, smooth muscle contraction in the lower urinary tract is an important target for the pharmacologic treatment of LUTS (alpha1-adrenoceptor antagonists, anticholinergics). Due to the limited effectiveness of current therapies, new options are urgently required. Current standard therapies (anticholinergics, alpha1-blockers) exclusively target single contractile systems. In contrast, investigations of the applicant demonstrated that the thromboxane receptor antagonist picotamide inhibits simultaneoulsy the paracrine, thromboxane-induced contraction, as well as the neurogenic, alpha1-adrenergic contraction in the human prostate. Many signs seem to show that picotamide and thromboxane may modulate smooth muscle tone in the detrusor of the urinary bladder. This might represent a promising, attractive strategy for the therapy of LUTS. Investigations in vitro and in vivo are subject of the present application.

• DFG Programme: Research Grants