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1 Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Department of Pharmacology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
2 Autonomic Neuroscience Institute, Royal Free and University College Medical School, London, United Kingdom
3 Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
4 Department of Clinical Veterinary Sciences, Ohio State University, Columbus, OH, USA
5 Department of Pharmacology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
6 GenitoUrinary Division, Roche Palo Alto, Palo Alto, CA, USA
* To whom correspondence should be addressed. E-mail: lbirder{at}pitt.edu.
Purinergic mechanisms appear to be involved in motor as well as sensory functions in the urinary bladder. ATP released from efferent nerves excites bladder smooth muscle; whereas ATP released from urothelial cells can activate afferent nerves and urothelial cells. In the present study we used immunohistochemical techniques to examine the distribution of purinoceptors in the urothelium, smooth muscle and nerves of the normal cat urinary bladder as well as possible changes in the expression of these receptors in cats with a chronic painful bladder condition termed feline interstitial cystitis (FIC) in which ATP release from the urothelium is increased. In normal cats, a range of P2X (P2X1, P2X2, P2X3, P2X4, P2X5, P2X6 and P2X7) and P2Y (P2Y1, P2Y2 and P2Y4) receptor subtypes were expressed throughout the bladder urothelium. In FIC cats, there is a marked reduction in P2X1 and loss of P2Y2 receptor staining. Both P2X3 and P2Y4 are present in nerves in normal cat bladder, and no obvious differences in staining were detected in FIC. Smooth muscle in the normal bladder did not exhibit P2Y receptor staining but did exhibit P2X (P2X2, P2X1) staining. In the FIC bladder smooth muscle, there was a significant reduction in P2X1 expression. These findings raise the possibility that purinergic mechanisms in the urothelium and bladder smooth muscle are altered in FIC cats. Since the urothelial cells appear to have a sensory function in the bladder it is possible that the plasticity in urothelial purinergic receptors is linked with the painful bladder symptoms in IC.
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