The molecular basis of urgency: regional difference of vanilloid receptor expression in the human urinary bladder.
OBJECTIVE
Treatments targeting vanilloid receptor TRPV1 are effective in some bladder disorders. Our aim was to determine the expression profiles of TRPV1 in regions of human bladder and test the hypothesis that there would be an upregulation of TRPV1 in mucosa of patients with bladder hypersensitivity but not idiopathic detrusor overactivity (IDO).


METHODS
Women with sensory urgency (SU), interstitial cystitis (IC), and IDO were investigated by videourodynamics and cystoscopy. Control biopsies were used for comparison. Biopsies were dissected into mucosa and muscle, and evaluated for TRPV1 mRNA expression using quantitative competitive RT-PCR (QC-RT-PCR).


RESULTS
TRPV1 mRNA from SU trigonal mucosa was significantly higher than control trigonal mucosa or SU bladder body mucosa. In contrast, in IDO patients, there was no difference between trigonal mucosa and body mucosa. In IC biopsies, RNA quality was substandard and unable to be used for analysis. The most striking finding was that TRPV1 mRNA expressed in SU trigonal mucosa was significantly inversely correlated with the bladder volume at first sensation of filling during cystometry. No such relationship was seen for IDO trigonal mucosa. No difference was seen in bladder body mucosa from any disease groups compared with age-matched control.


CONCLUSIONS
The symptoms of SU were associated with the increased expression of TRPV1 mRNA in the trigonal mucosa. No upregulation or regional differences of TRPV1 mRNA were seen in IDO patients. TRPV1 may play a role in SU and premature first bladder sensation on filling.
Liu
Lu
L
Department of Physiology & Pharmacology, School of Medical Sciences, University of New South Wales, Sydney, Australia.
Mansfield
Kylie J
KJ
Kristiana
Ika
I
Vaux
Kenneth J
KJ
Millard
Richard J
RJ
Burcher
Elizabeth
E
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001706:Biopsy; D005260:Female; D015870:Gene Expression / Q000502:physiology; D006801:Humans; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012677:Sensation; D050916:TRPV Cation Channels / Q000235:genetics* / Q000378:metabolism*; D015854:Up-Regulation / Q000502:physiology; D001743:Urinary Bladder / Q000294:innervation / Q000473:pathology / Q000502:physiology*; D053201:Urinary Bladder, Overactive / Q000473:pathology / Q000503:physiopathology*; D014563:Urodynamics / Q000235:genetics*; D019459:Urothelium / Q000502:physiology
D012333:RNA, Messenger; D050916:TRPV Cation Channels; C494482:TRPV1 protein, human