Investigating the associations of mucosal P2Y6 receptor expression and urinary ATP and ADP concentrations, with symptoms of overactive bladder

Aims. To characterise purinergic signalling in overactive bladder (OAB).

Methods. Mucosal biopsies were taken by flexible cystoscopy from patients with storage symptoms referred to Urology Departments of collaborating hospitals. Immunohistochemistry (n=12) and western blotting (n=28) were used to establish the qualitative and quantitative expression profile of P2Y6 in human mucosa. Participants from the general population provided a mid-stream urine sample. Bioluminescent assays were used to quantify ATP (n=66) and ADP (n=60) concentrations, which were normalised to creatinine (Cr) concentration. All participants completed a questionnaire (ICIQ-OAB) to score urinary symptoms of OAB.

Results. P2Y6 immunoreactivity, more prominent in the urothelium (co-localised with the uroepithelial marker pan-cytokeratin), was more greatly expressed in OAB compared to ageand gender-matched controls (BPH) without OAB symptoms. Mucosal P2Y6 was positively correlated only with incontinence (p=0.009). Both urinary ATP and its hydrolysis product, ADP, an agonist to P2Y6, were positively correlated with total OAB symptom score (p=0.010 and p=0.042, respectively).

Conclusions. The positive correlation of P2Y6 only with incontinence may indicate a different phenotype in OAB wet and warrants further investigation. Positive correlations of ATP and ADP with total OAB symptom score demonstrate upregulation in purinergic signalling in OAB; shown previously only in animal models. Further research is required to validate whether purinoceptors are indeed new therapeutic targets for this highly prevalent symptom complex.