Recent advances in basic science for overactive bladder

被引:37
作者
Kumar, V
Cross, RL
Chess-Williams, R
Chapple, CR
机构
[1] Royal Hallamshire Hosp, Urol Res Off, Sheffield S10 2JF, S Yorkshire, England
[2] Univ Sheffield, Dept Biomed Sci, Sheffield S10 2TN, S Yorkshire, England
关键词
detrusor overactivity; muscarinic; purinergic;
D O I
10.1097/01.mou.0000172393.52857.92
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
1002 ; 100201 ;
摘要
Purpose of review Detrusor overactivity is a relatively common yet embarrassing symptom complex with significant impact on quality of life. The mainstay of current pharmacological treatment involves the use of muscarinic receptor antagonists, but their therapeutic effectiveness is limited by a combination of limited efficacy and troublesome side effects and has recently been challenged by Herbison et al. Recognition of the limitations of existing therapy has started the search for pharmacotherapeutic agents acting on alternative pathways underlying detrusor overactivity with the intention of improving storage symptoms of urgency, frequency and urge incontinence. Recent findings Recent research has suggested that several transmitters may modulate bladder storage. However, no agents currently available, acting via mechanisms other than muscarinic receptors have entered clinical practice so far. It is clear that far from being a passive container for urine, the urothelium is a crucial area within the bladder wall and its functions are complex and only now beginning to be appreciated. The release of several neurotransmitters from urothelium in response to distension and its action on receptors on sensory neurons is being increasingly recognized. The role for this afferent stimulation on the micturition reflex is gradually gaining importance in the pathophysiology of detrusor overactivity. Summary In this article, the recent developments in basic science related to the pathogenesis and pharmacological basis for future drug targets for effective management of overactive bladder are discussed.
引用
收藏
页码:222 / 226
页数:5
相关论文
共 60 条
[1]   The intracellular pathway of the acetylcholine-induced contraction in cat detrusor muscle cells [J].
An, JY ;
Yun, HS ;
Lee, YP ;
Yang, SJ ;
Shim, JO ;
Jeong, JH ;
Shin, CY ;
Kim, JH ;
Kim, DS ;
Sohn, UD .
BRITISH JOURNAL OF PHARMACOLOGY, 2002, 137 (07) :1001-1010
[2]   M2 muscarinic receptor contributes to contraction of the denervated rat urinary bladder [J].
Braverman, AS ;
Luthin, GR ;
Ruggieri, MR .
AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY, 1998, 275 (05) :R1654-R1660
[3]   Release of vasoactive substances from endothelial cells by shear stress and purinergic mechanosensory transduction [J].
Burnstock, G .
JOURNAL OF ANATOMY, 1999, 194 :335-342
[4]  
Carbone A., 2003, European Urology Supplements, V2, P141, DOI 10.1016/S1569-9056(03)80559-6
[5]   Inhibition of human detrusor contraction by a urothelium derived factor [J].
Chaiyaprasithi, B ;
Mang, CF ;
Kilbinger, H ;
Hohenfellner, M .
JOURNAL OF UROLOGY, 2003, 170 (05) :1897-1900
[6]  
Chess-Williams RG, 2004, FUND CLIN PHARMACOL, V18, P32
[7]  
CHESSWILLIAMS R, 2002, J AUTON PHARMACOL, V21, P1
[8]   Partial outlet obstruction enhances modular autonomous activity in the isolated rat bladder [J].
Drake, MJ ;
Hedlund, P ;
Harvey, IJ ;
Pandita, RK ;
Andersson, KE ;
Gillespie, JI .
JOURNAL OF UROLOGY, 2003, 170 (01) :276-279
[9]   ATP is released from rabbit urinary bladder epithelial cells by hydrostatic pressure changes - a possible sensory mechanism? [J].
Ferguson, DR ;
Kennedy, I ;
Burton, TJ .
JOURNAL OF PHYSIOLOGY-LONDON, 1997, 505 (02) :503-511
[10]   M3 muscarinic receptors mediate contraction of human urinary bladder [J].
Fetscher, C ;
Fleichman, M ;
Schmidt, M ;
Krege, S ;
Michel, MC .
BRITISH JOURNAL OF PHARMACOLOGY, 2002, 136 (05) :641-643