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- Streng, T., et al.
(författare)
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Distribution and Function of the Hydrogen Sulfide-Sensitive TRPA1 Ion Channel in Rat Urinary Bladder
- 2008
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Ingår i: European Urology. - : Elsevier BV. - 0302-2838 .- 1873-7560. ; 53:2, s. 391-400
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To investigate the distribution of the transient receptor potential (TRP) A1 ion channel in the rat urinary bladder, and to study the effects of hydrogen sulfide (H2S) and known TRPA1 activators on micturition in conscious rats and on heterologously expressed ion channels. Methods: The expression of TRPA1 in urinary bladder was studied with fluorescence immunohistochemistry and real-time PCR in female Sprague-Dawley rats. Cystometric investigations were performed in conscious animals subjected to intravesical administration of sodium hydrogen sulfide (NaHS, donor of H2S), allyl isothiocyanate (AI), and cinnamaldehyde (CA). Fluorometric calcium imaging was used to study the effect of NaHS on human and mouse TRPA1 expressed in CHO cells. Results: TRPA1 immunoreactivity was found on unmyelinated nerve fibres within the urothelium, suburothelial space, and muscle layer as well as around blood vessels throughout the bladder. All TRPA1 immunoreactive nerves fibres also expressed TRPV1 immunoreactivity and vice versa. TRPA1 was also detected in urothelial cells at both transcriptional and protein levels. AI increased micturition frequency and reduced voiding volume. CA and NaHS produced similar changes in urodynamic parameters after disruption of the urothelial barrier with protamine sulfate. NaHS also induced calcium responses in TRPA1-expressing CHO cells, but not in untransfected cells. Conclusions: The expression of TRPA1 on C-fibre bladder afferents and urothelial cells together with the finding that intravesical TRPA1 activators initiate detrusor overactivity indicate that TRPA1 may have a role in sensory transduction in this organ. The study also highlights H2S as a TRPA1 activator potentially involved in inflammatory bladder disease. © 2007.
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| 2. |
- Bautista, D M, et al.
(författare)
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Pungent products from garlic activate the sensory ion channel TRPA1
- 2005
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Ingår i: Proceedings of the National Academy of Sciences. - : Proceedings of the National Academy of Sciences. - 1091-6490 .- 0027-8424. ; 102:34, s. 12248-12252
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Tidskriftsartikel (refereegranskat)abstract
- Garlic belongs to the Allium family of plants that produce organosulfur compounds, such as allicin and diallyl disulfide (DADS), which account for their pungency and spicy aroma. Many health benefits have been ascribed to Allium extracts, including hypotensive and vasorelaxant activities. However, the molecular mechanisms underlying these effects remain unknown. Intriguingly, allicin and DADS share structural similarities with allyl isothiocyanate, the pungent ingredient in wasabi and other mustard plants that induces pain and inflammation by activating TRPA1, an excitatory ion channel on primary sensory neurons of the pain pathway. Here we show that allicin and DADS excite an allyl isothiocyanate-sensitive subpopulation of sensory neurons and induce vasodilation by activating capsaicin-sensitive perivascular sensory nerve endings. Moreover, allicin and DADS activate the cloned TRPA1 channel when expressed in heterologous systems. These and other results suggest that garlic excites sensory neurons primarily through activation of TRPA1. Thus different plant genera, including Allium and Brassica, have developed evolutionary convergent strategies that target TRPA1 channels on sensory nerve endings to achieve chemical deterrence.
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