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Cannabinoid receptors 1 and 2 are associated with bladder dysfunction in an experimental diabetic rat model
Author(s) -
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
Publication year - 2013
Publication title -
bju international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.773
H-Index - 148
eISSN - 1464-410X
pISSN - 1464-4096
DOI - 10.1111/bju.12172
Subject(s) - medicine , endocrinology , carbachol , contraction (grammar) , agonist , detrusor muscle , cannabinoid receptor , antagonist , urinary bladder , cannabinoid , receptor , diabetes mellitus
Objective 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.Materials and Methods The bladder and dorsal root ganglion ( DRG ) were removed from diabetic rats and age‐matched controls 8–10 weeks after diabetes induction. Expression of CB1 and CB2 m RNA was studied using quantitative real‐time PCR and protein levels were determined by W estern blot analysis. The effect of increasing concentrations (0.1–100 μM) of the mixed CB1/CB2 agonist R (+)‐ WIN 55,212–2 ( WIN ), selective CB 1 antagonist ( AM 251) and selective CB 2 antagonist ( AM 630) on carbachol‐evoked contraction of bladder strips from control and diabetic rats was investigated. WIN ‐induced alterations of bladder strip contraction were then studied after pre‐incubation with AM 251 and AM 630.Results Diabetes induced decreased CB 1 protein and m RNA expression in both the bladder and DRG ( P < 0.05), while decreased CB 2 expression was observed in the bladder ( P < 0.05). 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. AM 630 and AM 251 had no effect on isolated detrusor muscle function. Moreover, pre‐incubation with AM 251 partially counteracted the effect of WIN on detrusor muscle contraction.Conclusion The results indicate that CB 1 and CB 2 are responsible for the pathogenesis of bladder dysfunction in diabetes mellitus and represent a viable target for pharmacological treatment of bladder cystopathy.