Cross-sensitization mechanisms between colon and bladder via transient receptor potential A1 stimulation in rats.
OBJECTIVE
The aim of this study was to analyze the mechanism underlying cross-sensitization between the colon and the bladder via activation of transient receptor potential A1 (TRPA1) channels.


METHODS
Using female Sprague-Dawley rats, polyethylene catheters were inserted into the colon between two ligations at the levels of 40 and 60 mm rostral to the anus and into the bladder. (1) We examined changes in colon and bladder activity after the application of allyl isothiocyanate (AI, 50 mM, 300 μl), a TRPA1 activator, into the colon or the bladder in an awake condition. Inhibitory effects of the pretreatment with HC-030031 (HC, 3 mg/kg), a TRPA1 inhibitor, on colon-to-bladder cross-sensitization induced by AI instilled in the colon were also investigated. (2) We examined Evans blue (EB) dye extravasation after TRPA1 stimulation in the colon or the bladder to evaluate vascular permeability due to tissue inflammation.


RESULTS
(1) Intercontraction intervals during continuous saline infusion into the bladder (0.04 ml/min) were significantly decreased after the intracolonic AI application, which significantly increased mean intracolonic pressure, indicative of colon-to-bladder cross-sensitization. The AI-induced colon-to-bladder cross-sensitization was completely prevented by the pretreatment with intravenous application of HC. On the other hand, mean intracolonic pressure was significantly decreased after the intravesical AI application, which significantly increased mean intravesical pressure. (2) EB dye extravasation was significantly increased in the AI-treated inflamed organs and also in the bladder following intracolonic AI treatment.


CONCLUSIONS
Colon-to-bladder cross-sensitization is mediated via TRPA1 stimulation in the colon, although TRPA1 expressed in the bladder does not seem to participate in bladder-to-colon cross-sensitization.
Department of Urology, Jikei University School of Medicine, Tokyo, Japan, a-furuta@rf7.so-net.ne.jp.
Akira
A
Furuta
Yasuyuki
Y
Suzuki
Takehito
T
Naruoka
Kouji
K
Asano
Shin
S
Egawa
Naoki
N
Yoshimura
D000083:Acetanilides / Q000494:pharmacology; D000283:Administration, Intravesical; D000818:Animals; D003092:Colitis / Q000139:chemically induced / Q000150:complications; D003106:Colon / Q000502:physiology*; D003556:Cystitis / Q000139:chemically induced / Q000150:complications; D005070:Evans Blue; D005119:Extravasation of Diagnostic and Therapeutic Materials / Q000209:etiology; D005260:Female; D017879:Isothiocyanates / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects*; D011312:Pressure; D011687:Purines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D000074025:TRPA1 Cation Channel; D050052:TRPC Cation Channels / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D001743:Urinary Bladder / Q000502:physiology*
C552888:2-(1,3-dimethyl-2,6-dioxo-1,2,3,6-tetrahydro-7H-purin-7-yl)-N-(4-isopropylphenyl)acetamide; D000083:Acetanilides; D017879:Isothiocyanates; D011687:Purines; D000074025:TRPA1 Cation Channel; D050052:TRPC Cation Channels; C480976:Trpa1 protein, rat; D005070:Evans Blue; C004471:allyl isothiocyanate