Subsensitivity of P2X but not vanilloid 1 receptors in dorsal root ganglia of rats caused by cyclophosphamide cystitis.
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.
Borvendeg
Sebestyen J
SJ
Rudolf-Boehm-Institute of Pharmacology and Toxicology, University of Leipzig, Haertelstrasse 16-18, D-04107 Leipzig, Germany.
Al-Khrasani
Mahmoud
M
Rubini
Patrizia
P
Fischer
Wolfgang
W
Allgaier
Clemens
C
Wirkner
Kerstin
K
Himmel
Herbert M
HM
Gillen
Clemens
C
Illes
Peter
P
D000818:Animals; D002118:Calcium / Q000378:metabolism; D003520:Cyclophosphamide / Q000633:toxicity; D018856:Cystitis, Interstitial / Q000139:chemically induced / Q000378:metabolism*; D015536:Down-Regulation; D005727:Ganglia, Spinal / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D010146:Pain / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011955:Receptors, Drug / Q000096:biosynthesis*; D018048:Receptors, Purinergic P2 / Q000096:biosynthesis*; D058476:Receptors, Purinergic P2X2; D050916:TRPV Cation Channels; D001743:Urinary Bladder / Q000294:innervation
D011955:Receptors, Drug; D018048:Receptors, Purinergic P2; D058476:Receptors, Purinergic P2X2; D050916:TRPV Cation Channels; C494484:TRPV1 receptor; D003520:Cyclophosphamide; D002118:Calcium