Vanilloid receptor expression suggests a sensory role for urinary bladder epithelial cells

Birder, Lori A.; Kanai, Anthony; Groat, William C. de; Kiss, Susanna; Nealen, Michele L.; Burke, Nancy A.; Dineley, Kirk E.; Watkins, Simon C.; Reynolds, Ian J.; Caterina, Michael J.

doi:10.1073/pnas.231243698

Cited by 473 publications

(419 citation statements)

References 26 publications

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“…A similar mechanism exists in the mouse urinary bladder, where urinary epithelial cell TRPV1 is required for hypoosmolarity-evoked release of ATP (37), which in turn appears to be detected by P2X3 (ATP-gated ion channel subtype three)-containing nerve terminals in the bladder wall (42). Alternative candidate heat-evoked signaling molecules include nitric oxide, which also undergoes TRPV1-dependent release from urinary epithelial cells (43), as well as prostaglandins and platelet-activating factor, which have been shown to be released from keratinocytes in response to UV radiation (44), extreme heating, oxidative stress (25), or, in human keratinocytes, capsaicin-evoked activation of TRPV1 (21). Biochemical analysis of supernatants from warmth-treated keratinocytes would allow the "soluble messenger" hypothesis to be tested experimentally, as would the analysis of thermosensation and thermoregulation in mice lacking TRPV4 selectively in keratinocytes.…”

Section: Discussionmentioning

confidence: 89%

Warm Temperatures Activate TRPV4 in Mouse 308 Keratinocytes

Chung¹,

Lee²,

Caterina³

2003

Journal of Biological Chemistry

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Mammalian survival requires constant monitoring of environmental and body temperature. Recently, several members of the transient receptor potential vanilloid (TRPV) subfamily of ion channels have been identified that can be gated by increases in temperature into the warm (TRPV3 and TRPV4) or painfully hot (TRPV1 and TRPV2) range. In rodents, TRPV3 and TRPV4 proteins have not been detected in sensory neurons but are highly expressed in skin epidermal keratinocytes. Here, we show that in response to warm temperatures (>32°C), the mouse 308 keratinocyte cell line exhibits nonselective transmembrane cationic currents and Ca 2؉ influx. Both TRPV3 and TRPV4 are expressed in 308 cells. However, the warmth-evoked responses we observe most closely resemble those mediated by recombinant TRPV4 on the basis of their electrophysiological properties and sensitivity to osmolarity and the phorbol ester, 4␣-phorbol-12,13-didecanoate. Together, these data support the notion that keratinocytes are capable of detecting modest temperature elevations, strongly suggest that TRPV4 participates in these responses, and define a system for the cell biological analysis of warmth transduction.The perception of ambient temperature is a physiological process critical to the maintenance of body temperature and the avoidance of painful or dangerous thermal extremes. Since the identification of the heat-sensing ion channel TRPV1 (1), 1 which is activated by temperatures above 42°C, there has been a significant focus on potential thermosensory functions for this and other ion channels of the transient receptor potential family. TRPV2 (2) and TRPV3 (3-5) were first described as heat transducers operative at very hot (Ͼ52°C) and moderately warm (Ͼ34°C) temperatures, respectively. TRPV4, which was originally identified as an osmosensory ion channel (6 -9), can also be activated by warm temperatures (Ͼ34°C) (10, 11). In addition, two TRP proteins outside of the TRPV subfamily, TRPM8 (12, 13) and ANKTM1 (ankyrin repeat/transmembrane-containing ion channel) (14), have been identified as cold-activated ion channels expressed in sensory neurons.In mammals, the skin is extremely important for the transduction of thermal information and its transmission to the central nervous system. Cutaneous thermosensation has been largely attributed to the sensory nerves that innervate the dermal and epidermal layers of the skin. Recent reports, however, have suggested the possibility that other skin components, most notably keratinocytes, might also participate in temperature sensation. TRPV1 and TRPV2 are highly expressed in distinct subsets of sensory neurons (2). In humans, TRPV3 is also expressed in sensory neurons (5). In contrast, attempts to detect TRPV4 (9, 10) and TRPV3 (3) at the protein level in rodent sensory neurons have been unsuccessful. Rather, immunohistochemical studies of mouse and rat skin have revealed that keratinocytes exhibit the greatest degree of cutaneous TRPV3 (3) and TRPV4 (10) expression. In addition, although peripheral sensory neurons ...

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Section: Discussionmentioning

confidence: 89%

Warm Temperatures Activate TRPV4 in Mouse 308 Keratinocytes

Chung¹,

Lee²,

Caterina³

2003

Journal of Biological Chemistry

Self Cite

261

211

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“…It remains to be determined whether this down-regulation is part of a compensatory mechanism or a consequence of LPS-induced death and shedding of urothelial cells. 17 As the urothelium works with underlying afferent nerves to detect the presence of irritant stimuli, 25 it will be of value to determine whether CD14, integrin ␣ 7, and MMP11 are part of the unique set of urothelial genes contrasting with those found in the bladder detrusor muscle. Ongoing experiments in this laboratory are determining which genes are uniquely expressed by each of the urinary bladder layers.…”

Section: Gene Up-regulation By Chronic Lps Stimulationmentioning

confidence: 99%

Gene Expression Profiling of Mouse Bladder Inflammatory Responses to LPS, Substance P, and Antigen-Stimulation

Saban

Nguyen

Hammond

et al. 2002

The American Journal of Pathology

110

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Inflammatory bladder disorders such as interstitial cystitis (IC) deserve attention since a major problem of the disease is diagnosis. IC affects millions of women and isClinical and animal models of acute and chronic urinary bladder inflammation have provided several lines of evidence suggesting a central role of mast cells, sensory nerves, and neurokinin (NK)-1 receptors. Fundamental work regarding the participation of sensory nerves and mast cells in cystitis provides indirect evidence, such as increased numbers of mast cells in the detrusor and submucosa, and morphological evidence of mast cell activation and degranulation. [1][2][3][4] In addition, the extensive tissue remodeling seen in some clinical forms of bladder inflammation such as interstitial cystitis, 4 along with increased urinary levels of histamine and tryptase 5 suggest a role for mast cells. Because both mast cells 6 -8 and NK-1 receptors are increased in bladder biopsies of interstitial cystitis (IC) patients, 9,10 it is tempting to propose a role for sensory peptides-mast cell communication in the pathogenesis of this disorder.Experimentally, we have used classical morphometric analysis and microarray technology to determine the role of mast cells, NK-1 receptors, and bacterial toxins in animal models of cystitis. Time-course experiments indicated early and late genes involved in bladder inflammatory responses. 11 The availability of mice genetically deficient in neurokinin-1 receptor (NK-1R Ϫ/Ϫ ) allowed us to propose a mandatory role of SP receptors in cystitis. 12 We also determined genes that depend on the presence of tissue mast cells for their expression by comparing inflammatory responses in mast cell-deficient (Kit W /

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“…Recent research, however, has indicated that VR1 is also distributed in some non-nervous tissues, such as liver, lungs, gastric epithelial cells [17] , bronchi [18] , bladder epithelium [19] , mast cells, skin cells [20] , and macrophages [21] . This finding suggests that VR1 might be involved in regulating a variety of physiological functions of different tissues and organs.…”

Section: Discussionmentioning

confidence: 99%

The protective effect of genistein postconditioning on hypoxia/reoxygenation-induced injury in human gastric epithelial cells

Zhang

et al. 2009

Acta Pharmacol Sin

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Vanilloid receptor expression suggests a sensory role for urinary bladder epithelial cells

Cited by 473 publications

References 26 publications

Warm Temperatures Activate TRPV4 in Mouse 308 Keratinocytes

Warm Temperatures Activate TRPV4 in Mouse 308 Keratinocytes

Gene Expression Profiling of Mouse Bladder Inflammatory Responses to LPS, Substance P, and Antigen-Stimulation

The protective effect of genistein postconditioning on hypoxia/reoxygenation-induced injury in human gastric epithelial cells

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