Differential expression of functional cannabinoid receptors in human bladder detrusor and urothelium.
OBJECTIVE
Although cannabinoid receptor expression has been demonstrated in human brain and other peripheral neuronal tissues, definitive expression of these receptors in the human bladder has not been reported. Consequently we investigated the expression of functional cannabinoid 1 and 2 receptors in human bladder detrusor and urothelium.


METHODS
Human bladders were micro-dissected for detrusor (6) and urothelium (8), and analyzed for cannabinoid 1 and 2 mRNA expression using real-time quantitative polymerase chain reaction, and for protein expression using immunohistochemistry and Western blot. Functional response of these receptors was tested by studying the effect of selective cannabinoid 1 and 2 agonists on nerve evoked smooth muscle contraction.


RESULTS
Quantitative polymerase chain reaction analysis revealed differential expression of cannabinoid 1 and 2 receptors in detrusor and urothelium. The expression of cannabinoid 1 and 2 receptor mRNA in urothelium was approximately 2-fold higher than in detrusor, although this was not significant (p >0.05). Cannabinoid 1 receptor mRNA expression was significantly higher than cannabinoid 2 receptor expression in the 2 tissue subtypes (p </=0.05). Expression at mRNA level was confirmed at the protein level by immunoreactivity and Western blot analysis. Activation of cannabinoid 1 and 2 receptors in human bladder attenuated the electrically evoked contraction of detrusor strips.


CONCLUSIONS
Together these findings suggest a physiological role of cannabinoid 1 and 2 receptors in the human bladder. Moreover, these results confirm the presence of functional cannabinoid 1 and 2 receptors in the human bladder, which can serve as a target for drugs acting on symptoms of interstitial cystitis/painful bladder syndrome.
Tyagi
Vikas
V
Department of Urology, University of Pittsburgh, Pittsburgh, Pennsylvania.
Philips
Brian J
BJ
Su
Ruthie
R
Smaldone
Marc C
MC
Erickson
Vickie L
VL
Chancellor
Michael B
MB
Yoshimura
Naoki
N
Tyagi
Pradeep
P
D000328:Adult; D000368:Aged; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D009130:Muscle, Smooth / Q000378:metabolism*; D043884:Receptor, Cannabinoid, CB1 / Q000096:biosynthesis*; D043885:Receptor, Cannabinoid, CB2 / Q000096:biosynthesis*; D001743:Urinary Bladder / Q000378:metabolism*; D019459:Urothelium / Q000378:metabolism
D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2