P2X3 knock-out mice reveal a major sensory role for urothelially released ATP.

摘要: The present study explores the possible involvement of a purinergic mechanism in mechanosensory transduction bladder using P2X3 receptor knock-out (P2X3−/−) and wild-type control (P2X3+/+) mice. Immunohistochemistry revealed abundant nerve fibers suburothelial plexus mouse that are immunoreactive to anti-P2X3. P2X3-positive staining was completely absent subepithelial P2X3−/− mice, whereas for calcitonin gene-related peptide vanilloid 1 receptors remained. Using novel superfused bladder–pelvic preparation, we detected release ATP proportional extent distension both P2X3+/+ although P2X3−/−bladder had an increased capacity compared with bladder. activity multifiber pelvic afferents progressively during gradual (at rate 0.1 ml/min). However, from mice showed attenuated response distension. Mouse P2X3+/+, but not P2X3−/−, were rapidly activated by intravesical injections P2X agonists (ATP or α,β-methylene ATP) subsequently augmented By contrast, antagonists [2′,3′-O-(2,4,6-trinitrophenyl)-ATP pyridoxal 5-phosphate 6-azophenyl-2′,4′-disulfonic acid] capsaicin distension-induced discharges afferents. These data strongly suggest major sensory role urothelially released acting via on subpopulation afferent fibers.