HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 294/5/F1146    most recent 00592.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Yu, Y. Articles by de Groat, W. C. PubMed PubMed Citation Articles by Yu, Y. Articles by de Groat, W. C.

Sensitization of pelvic afferent nerves in the in vitro rat urinary bladder-pelvic nerve preparation by purinergic agonists and cyclophosphamide pretreatment

Department of Pharmacology, University of Pittsburgh, Pittsburgh, Pennsylvania

Submitted 12 December 2007 ; accepted in final form 3 March 2008

Effects of purinergic agonists (,β-meATP and ATP) and cyclophosphamide-induced cystitis on bladder afferent nerve (BAN) activity were studied in an in vitro bladder-pelvic nerve preparation. Distension of the bladder induced spontaneous bladder contractions that were accompanied by multiunit afferent firing. Intravesical administration of 40 and 130 µM ,β-meATP increased afferent firing from 27 ± 3 to 53 ± 6 and 61 ± 2 spikes/s, respectively, but did not change the maximum amplitude of spontaneous bladder contractions. Electrical stimulation on the surface of the bladder elicited action potentials (AP) in BAN. ,β-meATP decreased the voltage threshold from 9.0 ± 1.2 to 3.5 ± 0.5 V (0.15-ms pulse duration) and increased the area of the APs (82% at 80-V stimulus intensity). These effects were blocked by TNP-ATP (30 µM). ATP (2 mM) applied in the bath produced similar changes in BAN activity. These effects were blocked by bath application of PPADS (30 µM). Neither TNP-ATP nor PPADS affected BAN activity induced by distension of the bladder. Cystitis induced by pretreatment of the rats with cyclophosphamide (100 mg/kg ip) increased afferent firing in response to isotonic bladder distension (10–40 cmH₂O), decreased the threshold, and increased the area of evoked APs. The increase in afferent firing at 10 cmH₂O intravesical pressure was reduced 52% by PPADS. These results indicate that purinergic agonists acting on P2X receptors and cystitis induced by cyclophosphamide can increase excitability of the BANs.

evoked action potentials; bladder mechanosensitive and chemosensitive afferent nerves; purinergic receptors