Differential Localizations of the Transient Receptor Potential Channels TRPV4 and TRPV1 in the Mouse Urinary Bladder

Abstract

S U M M A R Y We studied the localization and physiological functions of the transient receptor potential (TRP) channels TRPV1 (TRP vanilloid 1) and TRPV4 (TRP vanilloid 4) in the mouse bladder, because both channels are thought to be mechanosensors for bladder distention. RT-PCR specifically amplified TRPV4 transcripts from the urothelial cells, whereas TRPV1 transcripts were barely detectable. ISH experiments showed that TRPV4 transcripts were abundantly expressed in the urothelium, whereas TRPV1 transcripts were not detectable in the urothelial cells. Immunoblotting and IHC studies showed that TRPV4 proteins were mainly localized at the basal plasma membrane domains of the basal urothelial cells. In contrast, TRPV1-immunoreactivities were found not in the urothelial cells but in the nerve fibers that innervate the urinary bladder. In Ca 21-imaging experiments, 4a-phorbol 12,13-didecanoate, a TRPV4 agonist, and hypotonic stimuli induced significant increases in intracellular calcium ion concentration ([Ca 21 ] i ) in isolated urothelial cells, whereas capsaicin, a TRPV1 agonist, showed no marked effect on the cells. These findings raise the possibility that, in mouse urothelial cells, TRPV4 may contribute to the detection of increases in intravesical pressure related to the micturition reflex. (J Histochem Cytochem 57:277-287, 2009)

Expression and distribution of transient receptor potential (TRP) channels in bladder epithelium

“…However, urothelial expression has been questioned (17,18,59). In our studies, we detected relatively faint expression of TRPV1 by RT-PCR and Western blotting (Figs.…”

Inhibition of the cation channel TRPV4 improves bladder function in mice and rats with cyclophosphamide-induced cystitis

“…Recent research has identified TRPV4 as an important regulator of normal bladder function (12)(13)(14)(15)(16)25), but its involvement in the development of cystitis and the associated changes in bladder function was unknown. In this article, we show that the development of reduced functional bladder capacity and pollakisuria after cyclophosphamide treatment is strongly impaired in Trpv4 −/− mice, despite clear signs of severe hemorrhagic cystitis.…”

“…Recent research has shown that TRPV4, a cation channel of the transient receptor potential (TRP) superfamily (10,11), is highly expressed in the urothelial cell layer of the bladder, where it is implicated in sensing the filling state of the bladder (12)(13)(14)(15)(16). Importantly, Trpv4 −/− mice exhibited a lower voiding frequency and larger voided volume than wild type (WT) mice did.…”

Transient Receptor Potential Channels as Drug Targets: From the Science of Basic Research to the Art of Medicine

“…Capsaicin itself is not selective for TRPV1 either (see Szallasi and Blumberg, 1999). There is also a discrepancy between functional data: in particular, two independent groups were unable to replicate the capsaicin effects detected in human urothelial cells (Charrua et al, 2009b) using mouse (Yamada et al, 2009) and guinea pig (Xu et al, 2009b) urothelial cells, respectively (which may represent another striking species-related difference in TRP expression). Parenthetically, adding to the confusion, increased TRPV1 expression and capsaicin-evoked ATP release was recently reported in cultured human urothelial cells obtained from bladder biopsies of overactive bladder patients compared with control subjects .…”