Capsaicin receptor VR1 and ATP-gated ion channel P2X3 in human urinary bladder

Objectives To determine the presence, distribution and molecular forms of the vanilloid receptor VR1, and confirm the presence and distribution of the ATP-gated ion channel P2X(3) in the human urinary bladder. Materials and methods Normal urinary bladder tissues were obtained at postmortem from four subjects. Eight urinary bladder biopsies were also taken from patients with detrusor hyper-reflexia treated with intravesical resiniferatoxin. The specimens were studied using affinity-purified specific antibodies to VR1 and P2X(3) by Western blotting and immunocytochemistry, and compared with immunostaining using antibodies to the pan-neuronal marker PGP 9.5 and Schwann cell marker S-100. Results VR1- and P2X(3)-immunoreactive fine nerve fibres were scattered throughout the suburothelium of the normal bladder and cystoscopic biopsies, and traversed the muscle layer, They had a similar distribution to PGP 9.5-immunoreactive fibres, but there were fewer, suggesting localization in subsets of axons. Western blot: studies showed an expected 100-kDa VR1 protein and a P2X(3)-immunoreactive 66-kDa protein. Conclusion VR1 and P2X(3) are present in the human urinary bladder and may contribute to distinct pathophysiological states of bladder overactivity, in accord with their differential expression in sensory neurones, Intravesical vanilloids act via VR1 and are effective in the treatment of detrusor hyper-reflexia. P2X(3) may represent a selective therapeutic target for other causes of overactive bladder.