My laboratory is interested in understanding the complexities of urinary bladder epithelial (urothelial) cell function and urothelial cell-neuronal interactions. Our investigations have revealed that the urothelium, a stratified epithelial layer that lines the bladder lumen, might have the capacity to send signals to neighboring cells via the release of chemical mediators such as nitric oxide (NO) and ATP.
Our recent identification of a number of functional receptors/ion channels in bladder urothelial cells and the possible involvement of these receptors/ion channels in the release of mediators suggest that these cells exhibit specialized sensory and signaling properties. For example, we recently found that vanilloid receptor 1 (TRPV1) is expressed not only by afferent nerves that form close contacts with urothelial cells, but also by the urothelial cells themselves.
This arrangement would represent a departure from the conventional view of the urothelium as a simple barrier and provide further support for our speculation that the urothelium has “neuron-like” properties and that it may play a role in sensory mechanisms in the urinary bladder. Through an array of experimental approaches that include molecular biology (mouse knockouts; micro array analysis), measurement of transmitters (ATP, NO), Ca2+/confocal imaging techniques and in vivo monitoring of afferent and reflex bladder activity, our goals are to further characterize the properties of urothelial cells.
Elucidation of mechanisms impacting on urothelial function in addition to how pathology may impact on mechanisms of urothelial communication may provide important insight into targets for new therapies for the clinical management of lower urinary tract disorders.
Hanna-Mitchell AT, JM Beckel, S Barbadora, AJ Kanai, WC de Groat and LA Birder. Non-neuronal acetylcholine and urinary bladder urothelium. Life Sciences in press.
Chopra B, SE Barrick, S Meyers, JM Beckel, ML Zeidel, AP Ford, WC de Groat and LA Birder. Expression and function of bradykinin B1 and B2 receptors in normal and inflamed rat urinary bladder urothelium Journal of Physiology 562:859-871, 2005.
Birder LA, A Wolf-Johnston, CA Buffington, JR Roppolo, WC de Groat and AJ Kanai. Altered inducible nitric oxide synthase expression and nitric oxide production in the bladder of cats with feline interstitial cystitis. Journal of Urology 173:625-629, 2005.
Birder LA, HZ Ruan, B Chopra, Z Xiang, S Barrick, CA Buffington, JR Roppolo, AP Ford, WC de Groat and G Burnstock. Alterations in P2X and P2Y purinergic receptor expression in urinary bladder from normal cats and cats with interstitial cystitis. Am J Physiology 287:F1084-1091, 2004.
Birder LA, Y Nakamura, S Kiss, M Nealen, S Barrick, AJ Kanai, E Wang, G Ruiz, WC de Groat, G Apodaca, W Watkins and MJ Caterina. Altered bladder function in mice lacking the vanilloid receptor TRPV1. Nature Neuroscience 5(9):856-890, 2002.