Effects of TRPV4 cation channel activation on the primary bladder afferent activities of the rat.
OBJECTIVE
Transient receptor potential vanilloid 4 (TRPV4) may affect afferent pathways innervating the bladder. We investigated the effects of GSK1016790A (GSK) and RN1734, a TRPV4 agonist and antagonist, respectively, and P2X-purinoceptor antagonists (TNP-ATP and PPADS) on cystometry (CMG), and the effect of GSK on single afferent fiber activities (SAAs) of the rat bladder and its relationship with capsaicin (Cap)-sensitivity.


METHODS
Conscious female Sprague-Dawley rats were used for CMG measurements. In SAA measurements, under urethane anesthesia, SAA was identified by electrical stimulation of the pelvic nerve and by bladder distention. Cystometric parameters were measured before and after intravesical drug instillation. In SAA measurements, response with saline instillation served as baseline. Then, GSK was instilled three times, and finally Cap was instilled to investigate the relationship with Cap-sensitivity.


RESULTS
Intravesical GSK-instillation transiently decreased bladder capacity and voided volume, which were counteracted by RN1734, TNP-ATP, and PPADS. In SAA measurements, Aδ-fibers (n = 7) were not affected by either GSK or Cap. Based on the Cap-sensitivity, C-fibers could be divided into two subtypes: Cap-insensitive (n = 14) and Cap-sensitive (n = 8). In the Cap-insensitive C-fibers, GSK significantly increased the SAAs during the first instillation, but the increase attenuated with time, whereas GSK did not significantly affect the Cap-sensitive C-fibers.


CONCLUSIONS
The present results suggest that activation of TRPV4 in the bladder, probably urothelium, facilitates the micturition reflex by activation of the mechanosensitive, Cap-insensitive C-fibers of the primary bladder afferents in rats.
Department of Continence Medicine, The University of Tokyo Graduate School of Medicine, Tokyo, Japan.
Naoki
N
Aizawa
Jean-Jacques
JJ
Wyndaele
Yukio
Y
Homma
Yasuhiko
Y
Igawa
D000818:Animals; D002211:Capsaicin / Q000494:pharmacology; D004558:Electric Stimulation; D005260:Female; D007930:Leucine / Q000031:analogs & derivatives / Q000494:pharmacology; D023421:Models, Animal; D036421:Nerve Fibers, Unmyelinated / Q000502:physiology*; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology*; D058920:Purinergic P2X Receptor Antagonists / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013449:Sulfonamides / Q000494:pharmacology; D050916:TRPV Cation Channels / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*; D001743:Urinary Bladder / Q000294:innervation* / Q000502:physiology; D014554:Urination / Q000502:physiology*
C530602:N-(1-((4-(2-(((2,4-dichlorophenyl)sulfonyl)amino)-3-hydroxypropanoyl)-1-piperazinyl)carbonyl)-3-methylbutyl)-1-benzothiophene-2-carboxamide; D058920:Purinergic P2X Receptor Antagonists; C544743:RN 1734; D013449:Sulfonamides; D050916:TRPV Cation Channels; C486577:Trpv4 protein, rat; D007930:Leucine; D002211:Capsaicin