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PMID:11466438

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Citation

Vlaskovska, M, Kasakov, L, Rong, W, Bodin, P, Bardini, M, Cockayne, DA, Ford, AP and Burnstock, G (2001) P2X3 knock-out mice reveal a major sensory role for urothelially released ATP. J. Neurosci. 21:5670-7

Abstract

The present study explores the possible involvement of a purinergic mechanism in mechanosensory transduction in the bladder using P2X(3) receptor knock-out (P2X(3)-/-) and wild-type control (P2X(3)+/+) mice. Immunohistochemistry revealed abundant nerve fibers in a suburothelial plexus in the mouse bladder that are immunoreactive to anti-P2X(3). P2X(3)-positive staining was completely absent in the subepithelial plexus of the P2X(3)-/- 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 P2X(3)+/+ and P2X(3)-/- mice, although P2X(3)-/- bladder had an increased capacity compared with that of the P2X(3)+/+ 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 P2X(3)-/- mice showed an attenuated response to bladder distension. Mouse bladder afferents of P2X(3)+/+, but not P2X(3)-/-, were rapidly activated by intravesical injections of P2X agonists (ATP or alpha,beta-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 P2X(3) receptors on a subpopulation of pelvic afferent fibers.

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Keywords

Adenosine Triphosphate/analogs & derivatives; Adenosine Triphosphate/metabolism; Adenosine Triphosphate/pharmacology; Adenosine Triphosphate/secretion; Animals; Capsaicin/pharmacology; Dilatation; Electrophysiology; Immunohistochemistry; Male; Mechanoreceptors/metabolism; Mice; Mice, Knockout; Neurons, Afferent/classification; Neurons, Afferent/drug effects; Neurons, Afferent/physiology; Pelvis/innervation; Peripheral Nerves/drug effects; Peripheral Nerves/physiology; Purinergic P2 Receptor Agonists; Purinergic P2 Receptor Antagonists; Pyridoxal Phosphate/analogs & derivatives; Pyridoxal Phosphate/pharmacology; Receptors, Purinergic P2/deficiency; Receptors, Purinergic P2X3; Urinary Bladder/drug effects; Urinary Bladder/innervation; Urinary Bladder/metabolism; Urothelium/metabolism; Urothelium/secretion

Significance

Annotations

Gene product Qualifier GO ID GO term name Evidence Code with/from Aspect Notes Status


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