Subsensitivity of P2X but not vanilloid 1 receptors in dorsal root ganglia of rats caused by cyclophosphamide cystitis.

Abstract

The application of cyclophosphamide to rats was used to induce interstitial cystitis. Behavioural studies indicated a strong pain reaction that developed within 2 h and levelled off thereafter causing a constant pain during the following 18 h. Neurons prepared from L6/S1 dorsal root ganglia innervating the urinary bladder responded to the application of capsaicin or alpha,beta-methylene ATP (alpha,beta-meATP) with an increase of intracellular Ca2+ ([Ca2+]i). The [Ca2+]i responses to capsaicin were identical in the dorsal root ganglion cells of cyclophosphamide- and saline-treated rats, whereas alpha,beta-meATP induced less increase in [Ca2+]i in the cyclophosphamide-treated animals than in their saline-treated counterparts. Hence, alpha,beta-meATP-sensitive P2X3 and/or P2X2/3 receptors of L6/S1 dorsal root ganglion neurons were functionally downregulated during subacute pain caused by experimental cystitis. In contrast, capsaicin-sensitive vanilloid 1 receptors did not react to the same procedure. Thoracal dorsal root ganglia, not innervating the urinary bladder, were also unaltered in their responsiveness to alpha,beta-meATP by cyclophosphamide treatment.

• Authors: Sebestyen J Borvendeg, Mahmoud Al-Khrasani, Patrizia Rubini, Wolfgang Fischer, Clemens Allgaier, Kerstin Wirkner, Herbert M Himmel, Clemens Gillen, Peter Illes
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 474 Issue 1 Pg. 71-5 (Aug 01 2003) ISSN: 0014-2999 [Print] Netherlands
• PMID: 12909197 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Receptors, Drug
• Receptors, Purinergic P2
• Receptors, Purinergic P2X2
• TRPV Cation Channels
• TRPV1 receptor
• Cyclophosphamide
• Calcium

Topics

• Animals
• Calcium (metabolism)
• Cyclophosphamide (toxicity)
• Cystitis, Interstitial (chemically induced, metabolism)
• Down-Regulation
• Ganglia, Spinal (metabolism)
• Neurons (metabolism)
• Pain (metabolism)
• Rats
• Rats, Inbred Strains
• Receptors, Drug (biosynthesis)
• Receptors, Purinergic P2 (biosynthesis)
• Receptors, Purinergic P2X2
• TRPV Cation Channels
• Urinary Bladder (innervation)