RT Journal Article
SR Electronic
T1 P2X<sub>3</sub> Knock-Out Mice Reveal a Major Sensory Role for Urothelially Released ATP
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 5670
OP 5677
DO 10.1523/JNEUROSCI.21-15-05670.2001
VO 21
IS 15
A1 Mila Vlaskovska
A1 Lubomir Kasakov
A1 Weifang Rong
A1 Philippe Bodin
A1 Michelle Bardini
A1 Debra A. Cockayne
A1 Anthony P. D. W. Ford
A1 Geoffrey Burnstock
YR 2001
UL http://www.jneurosci.org/content/21/15/5670.abstract
AB The present study explores the possible involvement of a purinergic mechanism in mechanosensory transduction in the bladder using P2X3 receptor knock-out (P2X3−/−) and wild-type control (P2X3+/+) mice. Immunohistochemistry revealed abundant nerve fibers in a suburothelial plexus in the mouse bladder that are immunoreactive to anti-P2X3. P2X3-positive staining was completely absent in the subepithelial plexus of the P2X3−/− mice, whereas staining for calcitonin gene-related peptide and vanilloid receptor 1 receptors remained. Using a novel superfused mouse bladder–pelvic nerve preparation, we detected a release of ATP proportional to the extent of bladder distension in both P2X3+/+ and P2X3−/− mice, although P2X3−/−bladder had an increased capacity compared with that of the P2X3+/+ bladder. The activity of multifiber pelvic nerve afferents increased progressively during gradual bladder distension (at a rate of 0.1 ml/min). However, the bladder afferents from P2X3−/− mice showed an attenuated response to bladder distension. Mouse bladder afferents of P2X3+/+, but not P2X3−/−, were rapidly activated by intravesical injections of P2X agonists (ATP or α,β-methylene ATP) and subsequently showed an augmented response to bladder distension. By contrast, P2X antagonists [2′,3′-O-(2,4,6-trinitrophenyl)-ATP and pyridoxal 5-phosphate 6-azophenyl-2′,4′-disulfonic acid] and capsaicin attenuated distension-induced discharges in bladder afferents. These data strongly suggest a major sensory role for urothelially released ATP acting via P2X3 receptors on a subpopulation of pelvic afferent fibers.