Inhibition of urothelial P2X3 receptors prevents desensitization of purinergic detrusor contractions in the rat bladder. (25th March 2015)

• Record Type: Journal Article
• Authors: Ferguson, Andrew C.; Sutton, Broderick W.; Boone, Timothy B.; Ford, Anthony P.; Munoz, Alvaro
• Is Part Of: BJU international. Volume 116:Number 2(2015:Aug.)
• Page Start: 293
• Page End: 301
• Publication Date: 2015-03-25
• Subjects: Genitourinary organs -- Diseases -- Periodicals; Genitourinary organs -- Surgery -- Periodicals; Urology -- Periodicals; 616.6
• DOI: 10.1111/bju.13003
• Languages: English
• ISSNs: 1464-4096

Abstract

<abstract abstract-type="main" id="bju13003-abs-0001"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="bju13003-sec-0001" sec-type="section"> <title>Objectives</title> <p>To evaluate whether P2X3 receptors (P2X3R) are expressed in the bladder urothelium and to determine their possible function in modulating purinergic detrusor contractions in the rat urinary bladder.</p> </sec> <sec id="bju13003-sec-0002" sec-type="section"> <title>Materials and Methods</title> <p>The expression of urothelial receptors was determined using conventional immunohistochemistry in bladders from normal Sprague–Dawley rats. The urothelial layer was removed by incubation with protamine, and disruption of the urothelium was confirmed using haematoxylin and eosin staining on bladder sections. Open cystometry was used to determine the effects of both urothelial removal as well as intravesical application of a specific P2X3R antagonist on bladder properties from intact and protamine‐treated rats. Isometric contractile responses to potassium chloride (KCl) depolarization, electrical field stimulation (EFS) or chemical P2X activation were determined in normal and urothelium‐denuded bladder strips, with and without application of the P2X3R antagonist.</p> </sec> <sec id="bju13003-sec-0003" sec-type="section"> <title>Results</title> <p>Immunohistochemical staining showed high expression of P2X3R in the medial and basal layers of the urothelium. Removal of the urothelial layer disturbed normal bladder performance <italic>in vivo</italic> and eliminated the effects of the P2X3R antagonist on increasing the contractile interval and reducing the amplitude of voiding contractions. Removal of the urothelium did not affect bladder strip contractile responses to KCl depolarization or EFS. Pharmacological inhibition of P2X3R prevented desensitization to P2X‐mediated detrusor muscle contractions during EFS only in the strips with an intact urothelium. A concentration‐dependent, specific inhibition of P2X3R also prevented desensitization of purinergic contractile responses in intact bladder strips.</p> </sec> <sec id="bju13003-sec-0004" sec-type="section"> <title>Conclusions</title> <p>In the rat bladder, medial and basal urothelial cells express P2X3R, and specific inhibition of the receptor leads to a more hyporeflexive bladder condition. This pathway may involve P2X3R driving a paracrine amplification of ATP released from umbrella cells to increase afferent transmission in the sub‐urothelial sensory plexus and desensitization of P2X1‐mediated purinergic detrusor contractions.</p> </sec> </abstract>