Cannabinoid receptors 1 and 2 are associated with bladder dysfunction in an experimental diabetic rat model. (25th June 2013)

• Record Type: Journal Article
• Authors: Li, Yan; Sun, Yan; Zhang, Zhaocun; Feng, Xiaodi; Meng, Hui; Li, Shun; Zhu, Yaofeng; Chen, Shouzhen; Wang, Yang; Wang, Jun; Zhang, Deqing; Jiang, Xuewen; Li, Ning; Shi, Benkang
• Is Part Of: BJU international. Volume 112:Number 2(2013:Jul.)
• Page Start: E143
• Page End: E150
• Publication Date: 2013-06-25
• Subjects: Genitourinary organs -- Diseases -- Periodicals; Genitourinary organs -- Surgery -- Periodicals; Urology -- Periodicals; 616.6
• DOI: 10.1111/bju.12172
• Languages: English
• ISSNs: 1464-4096

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="bju12172-sec-0001" sec-type="section"> <title>Objective</title> <p> <list id="bju12172-list-0001" list-type="bullet"> <list-item> <p>To investigate diabetes‐associated changes in urinary bladder expression of cannabinoid receptors 1 and 2 (CB1 and CB2) and the functional role of CB agonists and antagonists in mediating phasic contractions of isolated bladder strips using a streptozotocin‐induced diabetic rat model.</p> </list-item> </list> </p> </sec> <sec id="bju12172-sec-0002" sec-type="section"> <title>Materials and Methods</title> <p> <list id="bju12172-list-0002" list-type="bullet"> <list-item> <p>The bladder and dorsal root ganglion (DRG) were removed from diabetic rats and age‐matched controls 8–10 weeks after diabetes induction.</p> </list-item> <list-item> <p>Expression of CB1 and CB2 mRNA was studied using quantitative real‐time PCR and protein levels were determined by Western blot analysis.</p> </list-item> <list-item> <p>The effect of increasing concentrations (0.1–100 μM) of the mixed CB1/CB2 agonist R(+)‐WIN 55, 212–2 (WIN), selective CB1 antagonist (AM251) and selective CB2 antagonist (AM630) on carbachol‐evoked contraction of bladder strips from control and diabetic rats was investigated.</p> </list-item> <list-item> <p>WIN‐induced alterations of bladder strip contraction were then studied after pre‐incubation with AM251 and AM630.</p> </list-item> </list> </p> </sec> <sec id="bju12172-sec-0003" sec-type="section"> <title>Results</title> <p> <list id="bju12172-list-0003" list-type="bullet"> <list-item> <p>Diabetes induced decreased CB1 protein and mRNA expression in both the bladder and DRG (<italic>P</italic> < 0.05), while decreased CB2 expression was observed in the bladder (<italic>P</italic> < 0.05).</p> </list-item> <list-item> <p>WIN decreased the amplitude, but not frequency, of carbachol‐induced phasic contractions of bladder strips in a concentration‐dependent manner and this effect was diminished in the diabetic state.</p> </list-item> <list-item> <p>AM630 and AM251 had no effect on isolated detrusor muscle function. Moreover, pre‐incubation with AM251 partially counteracted the effect of WIN on detrusor muscle contraction.</p> </list-item> </list> </p> </sec> <sec id="bju12172-sec-0004" sec-type="section"> <title>Conclusion</title> <p> <list id="bju12172-list-0004" list-type="bullet"> <list-item> <p>The results indicate that CB1 and CB2 are responsible for the pathogenesis of bladder dysfunction in diabetes mellitus and represent a viable target for pharmacological treatment of bladder cystopathy.</p> </list-item> </list> </p> </sec> </abstract>