Abstract:
:The contractile responses to capsaicin and anandamide, exogenous and endogenous agonists for transient receptor potential vanilloid receptor 1 (TRPV1), respectively, were investigated in muscle strips isolated from the rat urinary bladder. Capsaicin and anandamide produced concentration-dependent contractions of the muscle strips. The contractile response induced by capsaicin disappeared within approximately 20 min. In contrast, anandamide produced contractile responses lasting at least for 30 min. Capsaicin produced additive contractile responses in anandamide-treated muscle strips. The contractile response to anandamide was attenuated, but not abolished in strips desensitized by capsaicin. The response to capsaicin was abolished in the presence of a TRPV1 antagonist, N-(4-tertiarybutylphenyl)-4-(3-chlorphyridin-2-yl)tetrahydropyrazine-1(2H)-carbox-amide (BCTC), but not altered in the presence of either tetrodotoxin, atropine or indomethacin. In the presence of SR140333, a tachykinin NK(1) receptor antagonist or SR48968, an NK(2) receptor antagonist, the response to capsaicin was attenuated. The response to anandamide was partially attenuated in the presence of ONO8130, a prostanoid EP(1) receptor antagonist, URB597, a fatty-acid amide hydrolase inhibitor, BCTC, SR140333 or SR48968, and almost completely abolished by indomethacin. Neither tetrodotoxin, atropine, a cannabinoid CB(1) receptor antagonist, AM251, nor a cannabinoid CB(2) receptor antagonist, AM630, had any effect on the response to anandamide. These results indicate that capsaicin produces muscle contractions by stimulating the TRPV1 receptor, followed by release of neuropeptides that can activate tachykinin NK(1) and/or NK(2) receptors in the bladder and that the contractile response to anandamide is mediated at least in part by activation of prostanoid EP(1) receptors due to production of prostaglandins in addition to TRPV1 receptor activation.
journal_name
Eur J Pharmacoljournal_title
European journal of pharmacologyauthors
Saitoh C,Kitada C,Uchida W,Chancellor MB,de Groat WC,Yoshimura Ndoi
10.1016/j.ejphar.2007.05.016subject
Has Abstractpub_date
2007-09-10 00:00:00pages
182-7issue
1-3eissn
0014-2999issn
1879-0712pii
S0014-2999(07)00615-2journal_volume
570pub_type
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