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

Aim: 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.