The localization of cyclo‐oxygenase immuno‐reactivity (COX I‐IR) to the urothelium and to interstitial cells in the bladder wall

Abstract

Localized phasic contractions in the bladder wall (autonomous activity) have been hypothesized to be an integral part of a motor/sensory system contributing to bladder sensation. The sites responsible for generating this activity, the mechanisms involved in its propagation and modulation remain unknown. This phasic motor activity is modulated by exogenous prostaglandins. Therefore, analysis of the sites of prostaglandin production and action within the bladder wall may shed light on the mechanisms of generation and modulation of this phasic activity. In this paper we report the localization of immuno-reactivity indicative of the expression of cyclo-oxygenase enzyme type I (COX I-IR) within the bladder wall. Basically, three types of COX I-IR cell were identified: epithelial cells in the basal and intermediate layers of the urothelium, complex vimentin-positive and COX I-IR cells in the lamina propria and vimentin-negative COX I-IR cells in the lamina propria and on the surface of the inner muscle bundles. These vimentin-negative/COX I-IR cells appear to be in close apposition to a continuous network of vimentin-positive cells, which extends from the lamina propria into the inner muscle layers and subsequently into the outer muscle layers. However, the interstitial cells in this region might form a distinctly different sub-type. First, the interstitial cells in this region differ from those in the inner layer by their responsiveness to NO with a rise in cGMP. Two subtypes have been identified: cells on the surface of the muscle bundles and within the muscle bundles. Second, COX I-IR cells are not associated with the interstitial cells in the outer layers. The physiological significance for these apparent differences in the interstitial cell network is not clear. However, such differences are likely to reflect differences in the processes involved in their activation, modulation and control.

Release and inhibitory effects of prostaglandin D2 in guinea pig urinary bladder and the role of urothelium

“…In comparison the present results show a significantly higher release of prostaglandins from intact superfused bladders, suggesting that the release is not due to tissue damage, and that also under these conditions the urothelium is the major source of released prostaglandins with PGD 2 being comparable to PGE 2 . It is in agreement with a marked localization of cyclooxygenase 1 to the urothelium [17] and merits further investigations on the physiological conditions favoring PGD 2 release. Stretch and several autacoids have been shown to stimulate E and F prostaglandins release as well as thromboxane release in urinary bladders [8] and might be considered also in the regulation of PGD 2 production and release.…”

“…c o m / l o c a t e / b b a g e n detrusor motility [42]. It is well established that these prostanoids are produced locally within the bladder smooth muscle and mucosa in the human and other species [3,5,17,29]. Their production increases under various stimuli under pathological conditions such as bladder outlet obstruction [35,41], spinal cord injury induced bladder overactivity [36] and inflammation [43,50,51].…”

The cardiovascular and gastrointestinal adverse effects of cyclooxygenase inhibitors seems to be a major concern that restricts their use in the treatment of urinary bladder dysfunction

“…It was reported that exogenous PGs alter urinary bladder motor activity in in vitro and in vivo studies. A link between PGs and the muscarinic system has been described previously [6]. Nile et al [7] observed, in animal models, that ATP can activate PGE2 production by a complex mechanism, involving the purinergic receptors P2X and P2Y.…”

COX Inhibitors and Overactive Bladder: The Potential for Future Therapy

“…As mentioned previously, COX-1 and COX-2 are highly expressed in ICCs surrounding bundles of rabbit detrusor smooth muscle cells [20•]. They are found also in the urothelium and lamina propria of guinea pigs [24], and selective COX-1 and COX-2 inhibition, as well as nonselective inhibition of the PGE 2 receptor can abolish SRC [20]. The number of ICCs within the bladder wall and the degree of SRC are elevated in patients with overactive bladder [25].…”

“…ICCs surrounding detrusor smooth muscle bundles of the rabbit recently were shown to express COX-1 and COX-2, and both COX-1-and COX-2-selective blockade inhibited SRC in detrusor strips free of urothelium [20•]. In the guinea pig, COX-1 and COX-2 immunoreactivity was localized to cells in the basal urothelium, lamina propria, and muscle layer [24]. Although speculative at this time given the very few studies published, such information supports a link between ICCs, PGs, and SRC (Fig.…”