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Modulation of bladder alpha1-adrenergic receptor subtype expression by bladder outlet obstruction
Christian Hampel1, Paul C Dolber, Michael P Smith
1Department of Surgery (Urology), Duke University Medical Center and Department of Surgery, Durham Veterans Administration Medical Center, Durham, North Carolina 27710, USA.
The Journal of Urology
|February 8, 2002
Summary
Bladder outlet obstruction significantly increases alpha-1D adrenergic receptor (alpha1dAR) expression. Targeting alpha1dAR may offer new treatments for bladder irritative symptoms and overactivity.
Area of Science:
- Urology
- Pharmacology
- Molecular Biology
Background:
- Alpha-1 adrenergic receptor (alpha1AR) antagonists effectively treat bladder outlet obstruction (BOO) symptoms.
- The role of specific alpha1AR subtypes in relieving irritative symptoms of BOO is not fully understood.
Purpose of the Study:
- To investigate the involvement of bladder alpha1AR subtypes in the mechanisms of irritative symptom relief in BOO.
- To determine changes in alpha1AR subtype expression in response to BOO and detrusor hypertrophy.
Main Methods:
- Studied 42 rats with surgically induced BOO and sham controls.
- Quantified alpha1AR subtype mRNA using quantitative competitive reverse transcriptase-polymerase chain reaction.
- Determined alpha1AR protein expression via radioligand binding assays.
Main Results:
- Surgical obstruction led to significant detrusor hypertrophy and increased voiding frequency.
- Bladder alpha1AR density did not change overall, but subtype expression shifted dramatically.
- Alpha1aAR decreased from 70% to 23% mRNA, while alpha1dAR increased from 25% to 75% mRNA in obstructed bladders.
Conclusions:
- A significant increase in bladder alpha1dAR mRNA and protein expression was observed after 6 weeks of obstruction.
- Alpha1dARs exhibit higher affinity for norepinephrine compared to alpha1aAR and alpha1bAR.
- Targeting alpha1dAR presents a potential therapeutic strategy for managing irritative symptoms and detrusor overactivity in BOO.