Journal
EUROPEAN JOURNAL OF PHARMACOLOGY
Volume 740, Issue -, Pages 295-301Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ejphar.2014.07.018
Keywords
Menthol; Human colon; Motility; Calcium channels; TRPM8
Categories
Funding
- Minister dell'Istruzione, dell'Universita e della Ricerca, Italy [2007SSZMPK]
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Menthol is the major constituent of peppermint oil, an herbal preparation commonly used to treat nausea, spasms during colonoscopy and irritable bowel disease. The mechanism responsible for its spasmolytic action remains unclear. The aims of this study were to investigate the effects induced by menthol on the human distal colon mechanical activity in vitro and to analyze the mechanism of action. The spontaneous or evoked-contractions of the circular smooth muscle were recorded using vertical organ bath. Menthol (0.1 mM-30 mM) reduced, in a concentration-dependent manner, the amplitude of the spontaneous contractions without affecting the frequency and the resting basal tone. The inhibitory effect was not affected by 5-benzyloxytryptamine (1 mu M), a transient receptor potential-melastatin-8 channel antagonist, or tetrodotoxin (1 mu M), a neural blocker, or 1H-[1,2,4] oxacliazolo [4,3-a]quinoxalin-1-one (10 mu M), inhibitor of nitric oxide (NO)-sensitive soluble guanylyl cyclase, or tetraethylammonium (10 mM), a blacker of potassium (K+)-channels. On the contrary, nifeclipine (3 nM), a voltage-activated L-type Ca2+ channel blocker, significantly reduced the inhibitory menthol actions. Menthol also reduced in a concentration-dependent manner the contractile responses caused by exogenous application of Ca2+ (75-375 mu M) in a Ca2+-free solution, or induced by potassium chloride (KCl; 40 mM). Moreover menthol (1-3 mM) strongly reduced the electrical field stimulation (EFS)-evoked atropine sensitive contractions and the carbachol-contractile responses. The present results suggest that menthol induces spasmolytic effects in human colon circular muscle inhibiting directly the gastrointestinal smooth muscle contractility, through the block of Ca2+ influx through sarcolemma L-type Ca2+ channels. (C) 2014 Elsevier B.V. All rights reserved.
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