Contractile mechanisms coupled to TRPA1 receptor activation in rat urinary bladder.
TRPA1 is a member of the transient receptor potential (TRP) channel family present in sensory neurons. Here we show that vanilloid receptor (TRPV1) stimulation with capsaicin and activation of TRPA1 with allyl isothiocyanate or cinnamaldehyde cause a graded contraction of the rat urinary bladder in vitro. Repeated applications of maximal concentrations of the agonists produce desensitization to their contractile effects. Moreover, contraction caused by TRPA1 agonists generates cross-desensitization with capsaicin. The TRP receptor antagonist ruthenium red (10-100 microM) inhibits capsaicin (0.03 microM), allyl isothiocyanate (100 microM) and cinnamaldehyde (300 microM)-induced contractions in the rat urinary bladder. The selective TRPV1 receptor antagonist SB 366791 (10 microM) blocks capsaicin-induced contraction, but partially reduces allyl isothiocyanate- or cinnamaldehyde-mediated contraction. However, allyl isothiocyanate and cinnamaldehyde (10-1000 microM) completely fail to interfere with the specific binding sites for the TRPV1 agonist [(3)H]-resiniferatoxin. Allyl isothiocyanate or cinnamaldehyde-mediated contractions of rat urinary bladder, which rely on external Ca(2+) influx, are significantly inhibited by tachykinin receptor antagonists as well as by tetrodotoxin (1 microM) or indomethacin (1 microM). Allyl isothiocyanate-induced contraction is not changed by atropine (1 microM) or suramin (300 microM). The exposure of urinary bladders to allyl isothiocyanate (100 microM) causes an increase in the prostaglandin E(2) and substance P levels. Taken together, these results indicate that TRPA1 agonists contract rat urinary bladder through sensory fibre stimulation, depending on extracellular Ca(2+) influx and release of tachykinins and cyclooxygenase metabolites, probably prostaglandin E(2). Thus, TRPA1 appears to exert an important role in urinary bladder function.
Andrade
Edinéia Lemos
EL
Department of Pharmacology, Federal University of Santa Catarina, CCB, Campus Universitário Trindade, 88049-900 Florianópolis, SC, Brazil.
Ferreira
Juliano
J
André
Eunice
E
Calixto
João B
JB
D000171:Acrolein / Q000031:analogs & derivatives / Q000494:pharmacology; D000813:Anilides / Q000494:pharmacology; D000818:Animals; D017487:Ankyrins; D001665:Binding Sites / Q000187:drug effects; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism*; D002211:Capsaicin / Q000494:pharmacology; D002934:Cinnamates / Q000494:pharmacology; D004224:Diterpenes / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004336:Drug Antagonism; D066298:In Vitro Techniques; D017879:Isothiocyanates / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000502:physiology*; D009130:Muscle, Smooth / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012430:Ruthenium Red / Q000494:pharmacology; D000074025:TRPA1 Cation Channel; D050052:TRPC Cation Channels; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism; D001743:Urinary Bladder / Q000378:metabolism*
D000813:Anilides; D017487:Ankyrins; D015220:Calcium Channels; D002934:Cinnamates; D004224:Diterpenes; D017879:Isothiocyanates; C477659:N-(3-methoxyphenyl)-4-chlorocinnamanilide; D000074025:TRPA1 Cation Channel; D050052:TRPC Cation Channels; D050916:TRPV Cation Channels; C480976:Trpa1 protein, rat; C493922:Trpv1 protein, rat; D012430:Ruthenium Red; D000171:Acrolein; C024353:resiniferatoxin; C004471:allyl isothiocyanate; D002211:Capsaicin; C012843:cinnamaldehyde