Effects of menthol on circular smooth muscle of Human colon: Analysis of the mechanism of action.
Eur J Pharmacol. 2014 Jul 18;
Authors: Amato A, Liotta R, Mulè F
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 analyse the mechanism of action. The spontaneous or evoked- contractions of the circular smooth muscle were recorded using vertical organ bath. Menthol (0.1mM-30mM) 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 (1μM), a transient receptor potential-melastatin8 channel antagonist, or tetrodotoxin (1μM), a neural blocker, or 1H-[1,2,4] oxadiazolo [4,3-a]quinoxalin-1-one (10µM), inhibitor of nitric oxide (NO)- sensitive soluble guanylyl cyclase, or tetraethylammonium (10mM), a blocker of potassium (K(+))-channels. On the contrary, nifedipine (3nM), a voltage-activated L-type Ca(2+) channel blocker, significantly reduced the inhibitory menthol actions. Menthol also reduced in a concentration-dependent manner the contractile responses caused by exogenous application of Ca(2+) (75-375μM) in a Ca(2+)-free solution, or induced by potassium chloride (KCl; 40mM). Moreover menthol (1-3mM) 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 Ca(2+) influx through sarcolemma L-type Ca(2+) channels.
PMID: 25046841 [PubMed – as supplied by publisher]