Alterations in P2X and P2Y purinergic receptor expression in urinary bladder from normal cats and cats with interstitial cystitis

Abstract

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 (P2X(1), P2X(2), P2X(3), P2X(4), P2X(5), P2X(6), and P2X(7)) and P2Y (P2Y(1), P2Y(2), and P2Y(4)) receptor subtypes was expressed throughout the bladder urothelium. In FIC cats, there is a marked reduction in P2X(1) and loss of P2Y(2) receptor staining. Both P2X(3) and P2Y(4) 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 (P2X(2), P2X(1)) staining. In the FIC bladder smooth muscle, there was a significant reduction in P2X(1) expression. These findings raise the possibility that purinergic mechanisms in the urothelium and bladder smooth muscle are altered in FIC cats. Because 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.

Mechanisms of Disease: involvement of the urothelium in bladder dysfunction

“…feline interstitial cystitis) revealed an augmented stretch-evoked release of urothelium-derived ATP and changes in P2X and P2Y receptor profiles in urothelial cells. 29,50,51 This observation is consistent with similar findings in patients with interstitial cystitis. 43 These results suggest that urothelial sensor molecules exhibit plasticity in pathologic conditions, and might contribute to bladder pain syndromes.…”

Pirt reduces bladder overactivity by inhibiting purinergic receptor P2X3

“…2g-l). This result is consistent with the report that P2X3 receptors were primarily expressed in bladder nerves 14 . Importantly, Pirt-ir was shown to co-exist with P2X3-ir in nerve fibres (Fig.…”

“…GFP-tagged P2X3 was constructed by subcloning the full-length P2X3 cDNA into a pEGFP-N2 vector (Clontech). HA-tagged Pirt and PirtD (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14) were constructed by subcloning the full-length or truncated Pirt cDNA into the pCMV-HA vector (Clontech). Full-length P2X3 cDNA was also subcloned into pcDNA3.1 3.1/myc-His( À ) A (Invitrogen).…”

Localization of P2X and P2Y Receptors in Dorsal Root Ganglia of the Cat

“…The lack of immunoreactivity to P2X 5 -receptor antibodies might reflect that this antibody does not recognize cat proteins. However, this antibody has been successfully used to visualize P2X 5 receptors in the cat bladder urothelium (Birder et al 2004), suggesting that the lack of staining for P2X 5 receptors in the DRG is the result of an absence of receptors. ATP, in addition to other purines and pyrimidines, also evokes responses in nociceptors through P2Y metabotropic receptors.…”