Cyclophosphamide-Induced Bladder Inflammation Sensitizes and Enhances P2X Receptor Function in Rat Bladder Sensory Neurons
| Autor: | Khoa Dang, Gerald F. Gebhart, Michael X Cohen, Kenneth Lamb, Klaus Bielefeldt |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
Male
Patch-Clamp Techniques Cyclophosphamide Physiology Visceral Afferents Urinary Bladder Cystitis Interstitial Action Potentials Sensory system urologic and male genital diseases Splanchnic nerves Article Rats Sprague-Dawley Adenosine Triphosphate Ganglia Spinal medicine Animals Neurons Afferent Patch clamp Urothelium Receptor Sensitization Cell Size Hypogastric Plexus Urinary bladder Receptors Purinergic P2 business.industry General Neuroscience Splanchnic Nerves Carbocyanines Rats Disease Models Animal medicine.anatomical_structure Purines Receptors Purinergic P2X Cancer research Inflammation Mediators business Receptors Purinergic P2X3 Receptors Purinergic P2X2 medicine.drug |
| Zdroj: | Journal of Neurophysiology. 99:49-59 |
| ISSN: | 1522-1598 0022-3077 |
| Popis: | We studied sensitization of retrogradely labeled bladder sensory neurons and plasticity of P2X receptor function in a model of cystitis using patch-clamp techniques. Saline (control) or cyclophosphamide (CYP) was given intraperitoneally to rats on days 0, 2, and 4. On day 5, lumbosacral (LS, L6–S2) or thoracolumbar (TL, T12–L2) dorsal root ganglia were removed and dissociated. Bladders from CYP-treated rats showed partial loss of the urothelium and greater myeloperoxidase activity compared with controls. Bladder neurons from CYP-treated rats were increased in size (based on whole cell capacitance) compared with controls and exhibited lower activation threshold, increased action potential width, and greater number of action potentials in response to current injection or application of purinergic agonists. Most control LS bladder neurons (>85%) responded to ATP or α,β-metATP with a slowly desensitizing current; these agonists affected only half of TL neurons, producing predominantly fast/mixed desensitizing currents. CYP treatment increased the fraction of TL bladder neurons sensitive to purinergic agonists (>80%) and significantly increased current density in both LS and TL bladder neurons compared with control. Importantly, LS and TL neurons from CYP-treated rats showed a selective increase in the functional expression of heteromeric P2X2/3 and homomeric P2X3 receptors, respectively. Although desensitizing kinetics were slower in LS neurons from CYP-treated compared with control rats, recovery kinetics were similar. The present results demonstrate that bladder inflammation sensitizes and increases P2X receptor expression and/or function for both pelvic and lumbar splanchnic pathways, which contribute, in part, to the hypersensitivity associated with cystitis. |
| Databáze: | OpenAIRE |
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