Menthol Inhibits Detrusor Contractility Independently Of Trpm8 Activation

dc.creatorRamos-Filho A.C.S.
dc.creatorShah A.
dc.creatorAugusto T.M.
dc.creatorBarbosa G.O.
dc.creatorLeiria L.O.
dc.creatorDe Carvalho H.F.
dc.creatorAntunes E.
dc.creatorGrant A.D.
dc.date2014
dc.date2015-06-25T17:55:12Z
dc.date2015-11-26T14:36:34Z
dc.date2015-06-25T17:55:12Z
dc.date2015-11-26T14:36:34Z
dc.date.accessioned2018-03-28T21:40:29Z
dc.date.available2018-03-28T21:40:29Z
dc.identifier
dc.identifierPlos One. Public Library Of Science, v. 9, n. 11, p. - , 2014.
dc.identifier19326203
dc.identifier10.1371/journal.pone.0111616
dc.identifierhttp://www.scopus.com/inward/record.url?eid=2-s2.0-84910593976&partnerID=40&md5=05cb36af307bda16c611c9802215be6f
dc.identifierhttp://www.repositorio.unicamp.br/handle/REPOSIP/86782
dc.identifierhttp://repositorio.unicamp.br/jspui/handle/REPOSIP/86782
dc.identifier2-s2.0-84910593976
dc.identifier.urihttp://repositorioslatinoamericanos.uchile.cl/handle/2250/1248806
dc.descriptionAgonists such as icilin and menthol can activate the cool temperature-sensitive ion channel TRPM8. However, biological responses to menthol may occur independently of TRPM8 activation. In the rodent urinary bladder, menthol facilitates the micturition reflex but inhibits muscarinic contractions of the detrusor smooth muscle. The site(s) of TRPM8 expression in the bladder are controversial. In this study we investigated the regulation of bladder contractility in vitro by menthol. Bladder strips from wild type and TRPM8 knockout male mice (25-30 g) were dissected free and mounted in organ baths. Isometric contractions to carbachol (1 nM-30 μM), CaCl2 (1 μM to 100 mM) and electrical field stimulation (EFS; 8, 16, 32 Hz) were measured. Strips from both groups contracted similarly in response to both carbachol and EFS. Menthol (300 mM) or nifedipine (1 mM) inhibited carbachol and EFS-induced contractions in both wild type and TRPM8 knockout bladder strips. Incubation with the sodium channel blocker tetrodotoxin (1 μM), replacement of extracellular sodium with the impermeant cation N-Methyl-D-Glucamine, incubation with a cocktail of potassium channel inhibitors (100 nM charybdotoxin, 1 μM apamin, 10 mM glibenclamide and 1 μM tetraethylammonium) or removal of the urothelium did not affect the inhibitory actions of menthol. Contraction to CaCl2 was markedly inhibited by either menthol or nifedipine. In cultured bladder smooth muscle cells, menthol or nifedipine abrogated the carbachol or KCl-induced increases in [Ca2+]i. Intravesical administration of menthol increased voiding frequency while decreasing peak voiding pressure. We conclude that menthol inhibits muscarinic bladder contractions through blockade of L-type calcium channels, independently of TRPM8 activation.
dc.description9
dc.description11
dc.description
dc.description
dc.descriptionBBSRC; Higher Education Funding Council for England; HEFCE; Higher Education Funding Council for England; MRC; Higher Education Funding Council for England
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dc.languageen
dc.publisherPublic Library of Science
dc.relationPLoS ONE
dc.rightsaberto
dc.sourceScopus
dc.titleMenthol Inhibits Detrusor Contractility Independently Of Trpm8 Activation
dc.typeArtículos de revistas


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