Bladder Urothelial Cells From Patients With Interstitial Cystitis Have Increased Sensitivity To Carbachol

Main Category: Urology / Nephrology
Article Date: 30 Apr 2009 - 2:00 PDT

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UroToday.com - The presence of muscarinic receptors on bladder urothelial cells (BUC) suggests BUC may be a target for antimuscarinics. There are currently two recognized bladder hypersensory syndromes, overactive bladder and BPS/IC. Both syndromes overlap in symptomatology, urinary urgency (depending upon how urgency is defined), frequency, and nocturia. BPS/IC is strongly associated with pain and overactive bladder is not.

The urothelium and suburothelium actively participate in the sensory signaling of the bladder and express a range of receptors and release of neurotransmitters in response to distension and receptor activation. Muscarinic receptors are present on BUC and have been shown to mediate the release of adenosine triphosphate and nitric oxide, which in turn may activate afferent nerves or feedback on the BUC themselves.

Dr. Gopal Gupta and colleagues from Baltimore, Maryland designed a study to determine whether human BUC respond to muscarinic receptor activation and if so, whether this response is altered in BUC from patients with BPS/IC. Primary urothelial cell cultures were established from cystoscopic biopsies. Normal and BPS/IC urothelial cells were studied using calcium-imaging techniques as a means to monitor the response to muscarinic receptor activation with the agonist, carbachol. Changes in curves were measured in BPS/IC and normal bladder urothelial cells. Tolterodine was used to confirm the specificity of carbachol evoked increases in calcium ions.

The University of Maryland research team found that BPS/IC bladder urothelial cells, when compared to control BUC, were more sensitive to carbachol in increasing calcium ions. This was due to muscarinic rather than nicotinic activation as tolterodine, a non-specific muscarinic blocker without nicotinic effects, totally blocked carbachol's ability to increase calcium. The authors conclude that the greater sensitivity of BPS/IC BUC to carbachol suggests that BPS/IC pathophysiology may include alterations in urothelial cellular muscarinic signaling.

Gupta GN, Lu SG, Gold MS, Chai TC
Neurourol Urodyn. 2009 Mar 12. Epub ahead of print.
doi:10.1002/nau.20726

Written by UroToday.com Contributing Editor Philip M. Hanno, MD, MPH

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