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Function of the lower urinary tract in mice lacking alpha1d-adrenoceptor
Qin Chen1, Satoru Takahashi, Shan Zhong
1Department of Urology, Faculty of Medicine, University of Tokyo, Japan.
The Journal of Urology
|June 11, 2005
Summary
Mice lacking alpha-1D adrenergic receptors (AR) showed reduced urination frequency and increased voided volume, indicating this receptor subtype regulates bladder function. This supports alpha1d-AR blockers for treating urinary storage symptoms.
Area of Science:
- Urology
- Pharmacology
- Physiology
Background:
- Alpha-1 adrenergic receptor (AR) blockers are clinically used to treat lower urinary tract symptoms in men.
- These blockers are known to alleviate both voiding and storage symptoms.
Purpose of the Study:
- To investigate the role of the alpha1d-AR subtype in regulating lower urinary tract function.
- To analyze bladder function in mice lacking the alpha1d-AR using frequency/volume analysis and cystometry.
Main Methods:
- Studied 10 female alpha1d-knockout (KO) mice and 10 age-matched wild-type (WT) female mice.
- Recorded voiding frequency and volume for 48 hours, followed by awake, unrestrained filling cystometry.
- Quantified alpha1-AR subtype mRNA expression in bladder tissue using real-time PCR.
Main Results:
- Alpha1d-KO mice exhibited significantly lower daily voiding frequency (9.0 vs 15.9 in WT) and larger voided volume per void (0.24 vs 0.16 ml).
- Cystometry revealed increased bladder capacity (140%) and voided volume (146%) in alpha1d-KO mice compared to WT.
- Alpha1d-AR mRNA was undetectable in KO mice, while alpha1a and alpha1b-AR expression remained similar to WT mice.
Conclusions:
- The alpha1d-AR subtype plays a significant role in regulating bladder function.
- These findings provide theoretical support for the efficacy of alpha1-blockers targeting alpha1d-AR in managing benign prostatic obstruction-related storage symptoms.