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Urothelial neuron

J Y Liu, Y B Dai, X Li, K Cao, D Xie, Z T Tong, Z Long, H Xiao, M K Chen, Y L Ye, B Liu, J Tan, J Tang, Z Z Xu, Y Gan, Y H Zhou, F Deng, L Y He
Solute carrier family 12 member 5 (SLC12A5), an integral membrane KCl cotransporter, which maintains chloride homeostasis in neurons, is aberrantly expressed and involved in the tumorigenesis of certain cancers. However, the clinical significance and biological role of SLC12A5 in human bladder urothelial carcinoma (BUC) remains unclear. In this study, the expression of SLC12A5 was examined in clinical specimens of primary BUC and in BUC cell lines using quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR), western blot and immunohistochemistry (IHC)...
March 23, 2017: Cell Death & Disease
Ana Coelho, Tiago Antunes-Lopes, James Gillespie, Francisco Cruz
AIMS: To identify in the human bladder the structures which express the Beta-3 adrenoceptor (β3AR). METHODS: Human bladders from cadaveric organ donors (equally balanced in sex and age) were collected. Bladders were immediately fixed in paraformaldehyde and further processed for cryostat sectioning. Single and double immunohistochemistry was performed using antibodies against β3AR C-terminal, β3AR N-terminal, a pan-neuronal marker (β3-Tubulin) and markers of cholinergic (Vesicular Acetylcholine Transporter), adrenergic (Tyrosine Hidroxylase), and peptidergic (Calcitonin Gene-Related Peptide) nerve fibers...
February 10, 2017: Neurourology and Urodynamics
Hirosato Kanda, Buffie J Clodfelder-Miller, Jianguo G Gu, Timothy J Ness, Jennifer J DeBerry
Pelvic nerve (PN) bladder primary afferent neurons were retrogradely labeled by intraparenchymal (IPar) microinjection of fluorescent tracer or intravesical (IVes) infusion of tracer into the bladder lumen. IPar and IVes techniques labeled two distinct populations of PN bladder neurons differentiated on the basis of dorsal root ganglion (DRG) soma labeling, dye distribution within the bladder, and intrinsic electrophysiological properties. IPar (Fast blue)- and IVes (DiI)-labeled neurons accounted for 91.5% (378...
October 1, 2016: Brain Research
Kendall Morrison, Pia M Challita-Eid, Arthur Raitano, Zili An, Peng Yang, Joseph D Abad, Wendy Liu, Dawn Ratay Lortie, Josh T Snyder, Linnette Capo, Alla Verlinsky, Hector Aviña, Fernando Doñate, Ingrid B J Joseph, Daniel S Pereira, Karen Morrison, David R Stover
SLITRK6 is a member of the SLITRK family of neuronal transmembrane proteins that was discovered as a bladder tumor antigen using suppressive subtractive hybridization. Extensive immunohistochemistry showed SLITRK6 to be expressed in multiple epithelial tumors, including bladder, lung, and breast cancer as well as in glioblastoma. To explore the possibility of using SLITRK6 as a target for an antibody-drug conjugate (ADC), we generated a panel of fully human mAbs specific for SLITRK6. ADCs showed potent in vitro and in vivo cytotoxic activity after conjugation to Monomethyl Auristatin E or Monomethyl Auristatin F...
June 2016: Molecular Cancer Therapeutics
K-X Zhang, Y Matsui, C Lee, O Osamu, L Skinner, J Wang, A So, P S Rennie, W W Jia
Urothelial bladder cancer is the most common malignancy of the urinary tract. Although most cases are initially diagnosed as non-muscle-invasive, more than 80% of patients will develop recurrent or metastatic tumors. No effective therapy exists currently for late-stage metastatic tumors. By intravesical application, local administration of oncolytic Herpes Simplex virus (oHSV-1) can provide a promising new therapy for this disease. However, its inherent neurotoxicity has been a perceived limitation for such application...
2016: Gene Therapy
Anthony Kanai, Christopher Fry, Youko Ikeda, Florenta Aura Kullmann, Brian Parsons, Lori Birder
AIMS: To present a synopsis of the presentations and discussions from Think Tank I, "Implications for afferent-urothelial bidirectional communication" of the 2014 International Consultation on Incontinence-Research Society (ICI-RS) meeting in Bristol, UK. METHODS: The participants presented what is new, currently understood or still unknown on afferent-urothelial signaling mechanisms. New avenues of research and experimental methodologies that are or could be employed were presented and discussed...
February 2016: Neurourology and Urodynamics
Toby C Chai, Andrea Russo, Shan Yu, Ming Lu
The bladder mucosa is comprised of the multilayered urothelium, lamina propria (LP), microvasculature, and smooth muscle fibers (muscularis mucosae). The muscularis mucosae is not always present in the mucosa, and its presence is related to the thickness of the LP. Since there are no mucus secreting cells, "mucosa" is an imprecise term. Nerve fibers are present in the LP of the mucosa. Efferent nerves mediate mucosal contractions which can be elicited by electrical field stimulation (EFS) and various agonists...
October 2016: Autonomic Neuroscience: Basic & Clinical
Isabel Silva, Fátima Ferreirinha, Maria Teresa Magalhães-Cardoso, Miguel Silva-Ramos, Paulo Correia-de-Sá
PURPOSE: Deregulation of purinergic bladder signaling may contribute to persistent detrusor overactivity in patients with bladder outlet obstruction. Activation of uridine diphosphate sensitive P2Y6 receptors increases voiding frequency in rats indirectly by releasing adenosine triphosphate from the urothelium. To our knowledge this mechanism has never been tested in the human bladder. MATERIALS AND METHODS: We examined the role of the uridine diphosphate sensitive P2Y6 receptor on tetrodotoxin insensitive nonneuronal adenosine triphosphate and [(3)H]acetylcholine release from the human urothelium with the lamina propria of control organ donors and patients with benign prostatic hyperplasia...
October 2015: Journal of Urology
K-E Andersson
It is well established that in most species, exocytotic vesicular release of ATP from parasympathetic neurons contributes to contraction of the bladder. However, ATP is released not only from parasympathetic nerves, but also from the urothelium. During bladder filling, the urothelium is stretched and ATP is released from the umbrella cells thereby activating mechanotransduction pathways. ATP release can also be induced by various mediators present in the urine and and/or released from nerves or other components of the lamina propria...
September 2015: Autonomic Neuroscience: Basic & Clinical
Maria-Giuliana Vannucchi, Chiara Traini, Daniele Guasti, Giulio Del Popolo, Maria-Simonetta Faussone-Pellegrini
Urinary bladder voiding is a complex mechanism depending upon interplay among detrusor, urothelium, sensory and motor neurons and connective tissue cells. The identity of some of the latter cells is still controversial. We presently attempted to clarify their phenotype(s) in the human urinary bladder by transmission electron microscopy (TEM) and immunohistochemistry. At this latter aim, we used CD34, PDGFRα, αSMA, c-Kit and calreticulin antibodies. Both, TEM and immunohistochemistry, showed cells that, sharing several telocyte (TC) characteristics, we identified as TC; these cells, however, differed from each other in some ultrastructural features and immunolabelling according to their location...
October 2014: Journal of Cellular and Molecular Medicine
Naoki Yoshimura, Tomohiko Oguchi, Hitoshi Yokoyama, Yasuhito Funahashi, Satoru Yoshikawa, Yoshio Sugino, Naoki Kawamorita, Mahendra P Kashyap, Michael B Chancellor, Pradeep Tyagi, Teruyuki Ogawa
Bladder pain syndrome/interstitial cystitis is a disease with lower urinary tract symptoms, such as bladder pain and urinary frequency, which results in seriously impaired quality of life of patients. The extreme pain and urinary frequency are often difficult to treat. Although the etiology of bladder pain syndrome/interstitial cystitis is still not known, there is increasing evidence showing that afferent hyperexcitability as a result of neurogenic bladder inflammation and urothelial dysfunction is important to the pathophysiological basis of symptom development...
April 2014: International Journal of Urology: Official Journal of the Japanese Urological Association
Warren G Hill
Urine differs greatly in ion and solute composition from plasma and contains harmful and noxious substances that must be stored for hours and then eliminated when it is socially convenient to do so. The urinary tract that handles this output is composed of a series of pressurizable muscular compartments separated by sphincteric structures. With neural input, these structures coordinate the delivery, collection, and, ultimately, expulsion of urine. Despite large osmotic and chemical gradients in this waste fluid, the bladder maintains a highly impermeable surface in the face of a physically demanding biomechanical environment, which mandates recurring cycles of surface area expansion and increased wall tension during filling, followed by rapid wall compression during voiding...
March 6, 2015: Clinical Journal of the American Society of Nephrology: CJASN
Eric J Gonzalez, Lauren Arms, Margaret A Vizzard
Bladder pain syndrome (BPS)/interstitial cystitis (IC) is a chronic pain syndrome characterized by pain, pressure, or discomfort perceived to be bladder related and with at least one urinary symptom. It was recently concluded that 3.3-7.9 million women (>18 years old) in the United States exhibit BPS/IC symptoms. The impact of BPS/IC on quality of life is enormous and the economic burden is significant. Although the etiology and pathogenesis of BPS/IC are unknown, numerous theories including infection, inflammation, autoimmune disorder, toxic urinary agents, urothelial dysfunction, and neurogenic causes have been proposed...
2014: BioMed Research International
Jennifer J DeBerry, Erica S Schwartz, Brian M Davis
Urinary bladder pain is a primary symptom associated with interstitial cystitis/painful bladder syndrome. We used systemic injections of cyclophosphamide (CYP), an alkylating antineoplastic agent, to induce cystitis and examine the roles of 2 channels previously demonstrated to be required for inflammatory visceral hyperalgesia: transient receptor potential vanilloid-1 (TRPV1) and ankyrin-1 (TRPA1). Injection of CYP (100 mg/kg, i.p.) every other day for 5 days was accompanied by bladder edema and urothelial ulceration, but without significant plasma extravasation or infiltration of neutrophils...
July 2014: Pain
Inês Carneiro, M Alexandrina Timóteo, Isabel Silva, Cátia Vieira, Catarina Baldaia, Fátima Ferreirinha, Miguel Silva-Ramos, Paulo Correia-de-Sá
BACKGROUND AND PURPOSE: Despite the abundant expression of the UDP-sensitive P2Y6 receptor in urothelial cells and sub-urothelial myofibroblasts its role in the control of bladder function is not well understood. EXPERIMENTAL APPROACH: We compared the effects of UDP and of the selective P2Y6 receptor agonist, PSB0474, on bladder urodynamics in anaesthetized rats; the voided fluid was tested for ATP bioluminescence. The isolated urinary bladder was used for in vitro myographic recordings and [(3) H]-ACh overflow experiments...
July 2014: British Journal of Pharmacology
Niall P Hyland, Anna V Golubeva
Kalinichev et al., (2013) demonstrated that the GABAB receptor positive allosteric modulator, ADX71441, significantly improved micturition indices and cystometry variables in two models of overactive bladder, a disorder caused in part by urothelial dysfunction, increased excitability of the detrusor and abnormal functioning of neuronal circuits serving the micturition reflex. However, GABAB receptors are widely expressed at other peripheral sites, including the gastrointestinal tract. As well as their intimate anatomical relationship, the bladder and bowel share similarities in function, and the central processing and perception of afferent activity from each converge on the same brain regions...
February 12, 2014: British Journal of Pharmacology
L M McLatchie, J S Young, C H Fry
BACKGROUND AND PURPOSE: The aim of this study was to quantify and characterize the mechanism of non-neuronal ACh release from bladder urothelial cells and to determine if urothelial cells could be a site of action of anti-muscarinic drugs. EXPERIMENTAL APPROACH: A novel technique was developed whereby ACh could be measured from freshly isolated guinea pig urothelial cells in suspension following mechanical stimulation. Various agents were used to manipulate possible ACh release pathways in turn and to study the effects of muscarinic receptor activation and inhibition on urothelial ATP release...
July 2014: British Journal of Pharmacology
Adarsh P Shah, Amit Mevcha, Daniel Wilby, Anton Alatsatianos, John C Hardman, Steven Jacques, Joanne C Wilton
Urinary incontinence remains an important clinical problem worldwide, having a significant socio-economic, psychological, and medical burden. Maintaining urinary continence and coordinating micturition are complex processes relying on interaction between somatic and visceral elements, moderated by learned behavior. Urinary viscera and pelvic floor must interact with higher centers to ensure a functionally competent system. This article aims to describe the relevant anatomy and neuronal pathways involved in the maintenance of urinary continence and micturition...
November 2014: Clinical Anatomy
Björn L Isfoss, Christer Busch, Helena Hermelin, Anette T Vermedal, Marianne Kile, Geir J Braathen, Bernard Majak, Aasmund Berner
Survival after invasive bladder cancer has improved less than that of other common non-skin cancers. In many types of malignancy, treatment failure has been attributed to therapy-resistant stem-like cancer cells. Our aim was therefore to determine identities of stem cell marker-positive cells in bladder cancer tissue and to investigate possible associations between these cells and different forms of bladder neoplasia. We investigated tissue from 52 patients with bladder neoplasia and 18 patients with benign bladder conditions, from a cohort that had been previously described with regard to diagnosis and outcome...
April 2014: Virchows Archiv: An International Journal of Pathology
Tse-Yen Yang, Ling-I Hsu, Allen W Chiu, Yeong-Shiau Pu, Sheng-Hsin Wang, Ya-Tang Liao, Meei-Maan Wu, Yuan-Hung Wang, Chin-Hao Chang, Te-Chang Lee, Chien-Jen Chen
BACKGROUND: Arsenic is a well-documented carcinogen of human urothelial carcinoma (UC) with incompletely understood mechanisms. OBJECTIVES: This study aimed to compare the genome-wide DNA methylation profiles of arsenic-induced UC (AsUC) and non-arsenic-induced UC (Non-AsUC), and to assess associations between site-specific methylation levels and cumulative arsenic exposure. METHODS: Genome-wide DNA methylation profiles in 14 AsUC and 14 non-AsUC were analyzed by Illumina Infinium methylation27 BeadChip and validated by bisulfite pyrosequencing...
January 2014: Environmental Research
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