Capsaicin receptor VR1 and ATP-gated ion channel P2X(3) in human urinary bladder

Objectives To determine the presence, distribution and molecular forms of t he 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 postm ortem from four subjects. Eight urinary bladder biopsies were also taken fr om patients with detrusor hyper-reflexia treated with intravesical resinife ratoxin. The specimens were studied using affinity-purified specific antibo dies to VR1 and P2X(3) by Western blotting and immunocytochemistry, and com pared 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 thr oughout the suburothelium of the normal bladder and cystoscopic biopsies, a nd traversed the muscle layer, They had a similar distribution to PGP 9.5-i mmunoreactive fibres, but there were fewer, suggesting localization in subs ets 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, i n accord with their differential expression in sensory neurones, Intravesic al vanilloids act via VR1 and are effective in the treatment of detrusor hy per-reflexia. P2X(3) may represent a selective therapeutic target for other causes of overactive bladder.