Determination Of M2 And M3 Muscarinic Receptors In Bladder Mucosa Membrane Of Overactive Bladder And Interstitial Cystitis And Their Relationship With Clinical Symptoms.

Background: The Overactive bladder(OAB) and the Interstitial cystitis(IC) are all common and distressing conditions that have a significant impact on the quality of life of many people worldwide. And now, anticholinergics remain the first line for OAB in pharmacotherapy, and also have certain curative effect for IC. Of the five subtypes of muscarinic receptor, M2 and M3 are the main subtypes found in the bladder detrusor. Although the M2 receptors predominate in number, the M3 receptor directly mediates contraction. The main treatment for OAB is the use of anticholinergic drugs initially believed to inhibit the effect of parasympathetic acetylcholine (ACh) on the detrusor. With recent advances in our understanding of the basic science of the overactive bladder, the study found that the normal bladder mucous membrane also exist in M2 and M3 receptors in recent years, which is similar to the detrusor in number. Ruggieri et al.have shown M2-mediated contraction in a significant proportion of normal human bladders from organ donors, which was associated with an increased density of urothelial muscarinic receptors. Tong YC et al.recently studied in the diabetic rat bladder M2 receptor mRNA and protein are increased in the urothelium and the detrusor. However, the density of M2 and M3 muscarinic receptors in bladder mucosa membrane of OAB and IC and their relationship with clinical symptoms has yet to be established.Objective: Detect the density of M2 and M3 muscarinic receptors in bladder mucosa membrane of OAB and IC. Discussing the role of the M2 and M3 muscarinic receptors in bladder mucosa membrane.Methods:The specimens which are on top of the bladder mucous membrane obtained by cystourethroscopy bladder biopsy. Patients were divided into normal control group, IC group and OAB group. Detect the density of M2 and M3 muscarinic receptors in bladder mucosa membrane of the groups by real-time quantitative polymerase chain reaction. Evaluating the severity of lower urinary tract symptom in OAB patients by OAB Symptom Score(OABSS). Evaluating the severity of symptom in IC patients by the Pelvic Pain and Urgency/Frequency (PUF) questionnaire. Analyzed the difference between normal control group and OAB group or IC group by Mann-Whitney Test. Analyzed the relationship between the M2 and M3 of OAB group and OABSS by Spearman, and analyzed the relationship between the M2 and M3 of IC group and PUF.Results:The experimental study of 30 cases including normal control group(17), OAB group(5) and IC group(8). The density of M2RNA and M3RNA of normal control group respectively (8.12±15.16) and (3.02±13.07), The density of M2RNA and M3RNA of OAB group respectively (0.4±2.24)和(0.15±1.61), The density of M2RNA and M3RNA of IC group respectively (5.63±15.65)和(5.91±12.52). There was a significant decrease in the density of M2 and M3 muscarinic receptors in the overactive bladder group as compared with the normal controls (P<0.05). There was no difference in the density of M2 and M3 muscarinic receptors between the normal controls and the interstitial cystitis group(P>0.05).There were significant negative correlateion between the M2/M3 muscarinic receptors in the OAB group and the OABSS score(correlation coefficient respectively rm2=-0.949,rm3=-0.973,P<0.05). There were no significant correlateion between the M2/M3 muscarinic receptors in the IC group and the PUF score.Conclusions: The decrease of M2 and M3 muscarinic receptors in OAB group and their significant negative correlateion with OABSS score, suggesting the M2 and M3 receptors may be involved in the pathogenesis of OAB. The decrease of M2 and M3 muscarinic receptors density may be a form of self down regulatory mechanism to reduce the bladder sensitization in patients of OAB.