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Changes In M2 Receptor Expression On Human Bladder Urothelial Cells (BUC) In Response To Carbachol and Tolterodine
Emmanuel S Graham, Yan Sun, Julia Ahn*, Toby C Chai
University of Maryland, Baltimore, MD

Introduction: Recently Muscarinic (M2/M3) receptors have been identified on human bladder urothelium. We investigated the effects of carbachol, a muscarinic agonist and tolterodine (Detrol, Pfizer), a M2/M3 antagonist on the expression of M2 receptor transcript and protein levels from normal bladder (NB) and interstitial cystitis (IC) patients.
Methods: BUC were cultured from cystoscopic biopsies from 5 NB and 5 IC patients. Cells were subjected to three conditions: no-treatment, 1mM carbachol for 48-hours, and 1mM carbachol with 1uM tolterodine for 48 hours. Real time PCR and Western Blot analyses were performed for M2 receptor mRNA and protein expression respectively.
Results: M2 mRNA increased 8.5 fold and 5.2 fold in NB and IC cells respectively. On Western blot analyses, NB cells did not have a significant increase in M2 protein, but IC cells did in response to carbachol (2.5-fold increase, p=0.011, see Figure). A representative Western from 1 IC patient is also shown in the Figure. Tolterodine blunted M2- protein expression.
Conclusions: Carbachol induced significant increases in M2-protein expression in IC BUC. While anti-muscarinics are not effective in treating IC symptoms, the changes in M2-protein expression in IC BUC suggest that urothelial cells represent a potential therapeutic target in the bladder.

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