Regional differences in sensory innervation and suburothelial interstitial cells in the bladder neck and urethra.
ABSTRACT To identify and characterize possible structural specialisations in the wall of the lower urinary tract (LUT) in the region of the bladder urethral junction (BUJ), with the specific objective of identifying regional variations in sensory nerve fibres and interstitial cells (ICs).
The bladder base and urethra was removed from five male guinea pigs killed by cervical dislocation. Tissue pieces were incubated in Krebs' solution at 36 degrees C, gassed with 95% O(2) and 5% CO(2), fixed in 4% paraformaldehyde and processed for immunohistochemistry. The nonspecific marker vimentin and the general neuronal marker protein gene product (PGP) 9.5 were used to identify ICs and nerve fibres, respectively. Specific antibody binding was visualized using the appropriate secondary antibodies.
The wall of the LUT in the region immediately between the bladder base and the urethra, the BUJ, differed in its cellular composition relative to the adjacent areas. PGP-positive (PGP(+)) nerve fibres, presumptive afferent fibres, lay within the urothelium running between the epithelial cells. There were two general nerve patterns: branching fibres with no varicosities, and complex fibres with varicosities. Fibre collaterals with varicosities exited the urothelium and occupied the space under the urothelium adjacent to the layer of suburothelial ICs. The latter, lamina propria and around the muscle bundles were identified using vimentin (vim(+)). In the base a few vim(+) cells were also PGP(+). In the region of the BUJ there was a decrease in the amount of smooth muscle. In this region, below the lamina propria, there was an area densely populated with vim(+)/PGP(+) ICs. Nerve fibres ran between the cells in this region.
These structural specialisations within the urothelium and deeper layers of the BUJ suggest that they might be associated with specific functions. The localized highly branched network of the putative afferent nerves suggests the presence of a local axonal reflexes involving possible cross-talk between the urothelium and suburothelial layer. The function of the specialized region of ICs is not known and must await further information on the functional properties of this novel cell type. These observations show further the cellular heterogeneity of the cells in the LUT and the complexity of the structures. One of the major current challenges in functional urology is to understand the relationships between these novel structures and overall bladder and urethral function.
- SourceAvailable from: Michael R Ruggieri[show abstract] [hide abstract]
ABSTRACT: The urothelium is a multifunctional tissue that not only acts as a barrier between the vesical contents of the lower urinary tract and the underlying tissues but also acts as a sensory organ by transducing physical and chemical stresses to the attendant afferent nervous system and underlying smooth muscle. This review will consider the nature of the stresses that the urothelium can transduce; the transmitters that mediate the transduction process; and how lower urinary pathologies, including overactive bladder syndrome, painful bladder syndrome and bacterial infections, are associated with alterations to this sensory system. In particular, the role of muscarinic receptors and the TRPV channels system will be discussed in this context. The urothelium also influences the contractile state of detrusor smooth muscle, both through modifying its contractility and the extent of spontaneous activity; potential pathways are discussed. The potential role that the urothelium may play in bladder underactivity is introduced, as well as potential biomarkers for the condition that may cross the urothelium to the urine. Finally, consideration is given to vesical administration of therapeutic agents that influence urinary tract function and how the properties of the urothelium may determine the effectiveness of this mode of delivery.Neurourology and Urodynamics 01/2012; 31(3):293-9. · 2.67 Impact Factor
- [show abstract] [hide abstract]
ABSTRACT: Traditionally, sensory signaling in the urinary bladder has been largely attributed to direct activation of bladder afferents. There is substantive evidence that sensory systems can be influenced by non-neuronal cells, such as the urothelium, which are able to respond to various types of stimuli that can include physiological, psychological and disease-related factors. The corresponding release of chemical mediators (through activation of a number of receptors/ion channels) can initiate signaling mechanisms between and within urothelial cells, as well as other cell types within the bladder wall including bladder nerves. However, the mechanisms underlying how various cell types in the bladder wall respond to normal filling and emptying, and are challenged by a variety of stressors (physical and chemical) are still not well understood. Alterations or defects in signaling mechanisms are likely to contribute to the pathophysiology of bladder disease with symptoms including urinary urgency, increased voiding frequency and pain. This review will discuss some of the components involved in control of lower urinary tract function, with an emphasis on the sensor and transducer roles of the urothelium.International Journal of Urology 10/2012; · 1.73 Impact Factor
- [show abstract] [hide abstract]
ABSTRACT: In this paper, a general introduction is given, presenting the overactive bladder syndrome (OAB) and its impact on the quality of life and economical burden in patients affected. Moreover, the anatomy, physiology and histology of the lower urinary tract are discussed, followed by a brief overview on the possible role of prostaglandin (PG) and phosphodiesterase type 5 (PDE5) in the urinary bladder. The current literature on the role and distribution of PGE2 and its receptors in the urinary bladder is discussed. In both animal models and in human studies, high levels of signaling molecules such as PG and cGMP have been implicated, in decreased functional bladder capacity and micturition volume, as well as in increased voiding contraction amplitude. As a consequence, inhibition of prostanoid production, the use of prostanoid receptor antagonists, or PDE inhibitors might be a rational way to treat patients with detrusor overactivity. Similarly, prostanoid receptor agonists, or agents that stimulate their production, might have a function in treating bladder underactivity.Nephro-urology monthly. 09/2013; 5(4):934-945.