Contractile properties of the pig bladder mucosa in response to neurokinin A: a role for myofibroblasts?

Abstract

Background and purpose: The bladder urothelium is now known to have active properties. Our aim was to investigate the contractile properties of the urinary mucosa in response to the tachykinin neurokinin A (NKA) and carbachol. Experimental approach: Discrete concentration-response curves for carbachol and NKA were obtained in matched strips of porcine detrusor, mucosa and intact bladder, suspended in organ baths. The effects of inhibitors and tachykinin receptor antagonists were studied on NKA-mediated contractions in mucosal strips. Intact sections of bladder and experimental strips were processed for histology and immunohistochemistry. Key results: All types of strips contracted to both carbachol and NKA. Mucosal responses to NKA (pD 2 7.2) were higher than those in intact strips and were inhibited by the NK 2 receptor antagonist SR48968 (pK B 9.85) but not the NK 1 receptor antagonist SR140333, tetrodotoxin or indomethacin. Immunostaining for smooth muscle actin and vimentin occurred under the urothelium and on blood vessels. Desmin immunostaining and histological studies showed only sparse smooth muscle to be present in the mucosal strips. Removal of smooth muscle remnants from mucosal strips did not alter the responses to NKA. Conclusions and implications:This study has shown both functional and histological evidence for contractile properties of the mucosa, distinct from the detrusor. Mucosal contractions to NKA appear to be directly mediated via NK 2 receptors. The main cell type mediating mucosal contractions is suggested to be suburothelial myofibroblasts. Mucosal contractions may be important in vivo for matching the luminal surface area to bladder volume.

Urothelial/Lamina Propria Spontaneous Activity and the Role of M3 Muscarinic Receptors in Mediating Rate Responses to Stretch and Carbachol

“…In a recent study we showed that isolated strips of U&LP from the pig bladder dome can also contract in response to neurokinin A and muscarinic receptor stimulation, the responses to NKA being mediated via NK2 receptors (Sadananda et al, 2008). These tissues from the dome of the bladder also develop spontaneous phasic contractions.…”

“…In addition to releasing ATP and other mediators, the U&LP of the pig bladder (Sadananda et al, 2008) and the lamina propria of the rabbit urethra (Mattiasson et al, 1985, Zygmunt et al, 1993) display contractile properties and have been shown to contract in response to a number of agonists. It is presently unclear which specific cell types mediate contraction, but it has been suggested that myofibroblasts may be involved (Sadananda et al, 2008).…”

“…It is presently unclear which specific cell types mediate contraction, but it has been suggested that myofibroblasts may be involved (Sadananda et al, 2008). In addition, it has been reported that spontaneous contractions of intact bladder strips may be linked to the U&LP (Akino et al, 2008).…”

Adrenoceptor Function and Expression in Bladder Urothelium and Lamina Propria

“…Tension responses to neurokinin A and carbachol are present after fine dissection and removal of smooth muscle from the preparations and it has been suggested that myfibroblasts may be involved. 5,8 In addition, spontaneously generated electrophysiological events have been observed in myofibroblasts located within the lamina propria. 26 The function of this contractile activity is also uncertain.…”

“…This inner region of the bladder wall has a barrier function, but also when stretched it releases a number of factors that influence detrusor contraction and afferent nerve sensitivity. 3 In addition, the urothelium with lamina propria from the dome of the pig bladder 4,5 and also strips of lamina propria from the rabbit urethra 6,7 have been shown to contract to agonists such as carbachol, neurokinin A and noradrenaline. Isolated strips of urothelium with lamina propria also develop spontaneous contractile activity, with carbachol and also stretch-induced release of acetylcholine mediating increases in spontaneous contractile frequency via M 3 receptors.…”