P2X3Knock-Out Mice Reveal a Major Sensory Role for Urothelially Released ATP
| Autor: | Anthony P.D.W. Ford, Weifang Rong, Philippe Bodin, Lubomir Kasakov, Geoffrey Burnstock, Michelle Bardini, Debra A. Cockayne, Mila Vlaskovska |
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| Rok vydání: | 2001 |
| Předmět: |
Male
Purinergic P2 Receptor Agonists endocrine system medicine.medical_specialty Pathology Urinary Bladder TRPV1 In Vitro Techniques Biology urologic and male genital diseases Pelvis Mice chemistry.chemical_compound Adenosine Triphosphate Internal medicine Purinergic P2 Receptor Antagonists medicine Animals heterocyclic compounds Neurons Afferent Peripheral Nerves ARTICLE Receptor Mice Knockout Urinary bladder urogenital system Receptors Purinergic P2 musculoskeletal neural and ocular physiology General Neuroscience Purinergic receptor Dilatation Immunohistochemistry Electrophysiology body regions Endocrinology medicine.anatomical_structure chemistry Capsaicin Calcitonin Pyridoxal Phosphate Knockout mouse Urothelium Mechanoreceptors Receptors Purinergic P2X3 |
| Zdroj: | The Journal of Neuroscience. 21:5670-5677 |
| ISSN: | 1529-2401 0270-6474 |
| DOI: | 10.1523/jneurosci.21-15-05670.2001 |
| Popis: | 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 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 P2X(3) receptors on a subpopulation of pelvic afferent fibers. |
| Databáze: | OpenAIRE |
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