The differential contractile responses to capsaicin and anandamide in muscle strips isolated from the rat urinary bladder

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.

Differential Effects of Botulinum Neurotoxin A on Bladder Contractile Responses to Activation of Efferent Nerves, Smooth Muscles and Afferent Nerves in Rats

“…8,14 However, BoNT/A action on other compartments, such as smooth muscle and blood vessels, cannot be completely excluded. Results demonstrated that longer incubation (overnight) with BoNT/A was needed to inhibit capsaicin induced contractions ( fig.…”

“…We previously reported that capsaicin induces bladder smooth muscle contraction by stimulating the TRPV1 receptor expressed on afferent nerve terminals, followed by the release of neuropeptides that can activate tachykinin NK1 and/or NK2 receptors on bladder smooth muscle. 8 Therefore, to examine the effect of BoNT/A on afferent nerve terminals we evaluated changes in capsaicin (1 M) induced contractions.…”

HCl-activated neural and epithelial vanilloid receptors (TRPV1) in cat esophageal mucosa

“…Diffusion of HCl across the mucosa is unlikely to be responsible for the reduction in contraction, because the supernatant remained at pH 7.4 throughout the experiment. Similarly, diffusion of capsaicin across the mucosa is unlikely to play a role in reducing the contraction, because capsaicin contracts circular muscle (27,29,52), the supernatant of the capsaicinfilled sac inhibited circular muscle contraction, and, in addition, the contraction was almost completely restored by a PAF antagonist. PAF, however, is produced with substance P and CGRP; Fig.…”

TRPA1-dependent regulation of bladder detrusor smooth muscle contractility in normal and type I diabetic rats

“…They involve the release from TRPA1- and TRPV1-expressing sensory afferents of neurotransmitters which have a contractile action on DSM: prostaglandins and substance P (SP) with TRPA1 activation (6), and SP and calcitonin gene-related peptide (CGRP) with TRPV1 activation (22,23,24). The presence of a SP component in the EFS-contractions upon CAP-mediated TRPV1 stimulation was demonstrated by using tachykinin receptor antagonists (23).…”