The actions of peppermint oil and menthol on calcium channel dependent processes in intestinal, neuronal and cardiac preparations

Abstract

The activities of menthol and peppermint oil were determined in guinea-pig ileal smooth muscle, in rat and guinea-pig atrial and papillary muscle, in rat brain synaptosomes and in chick retinal neurones by pharmacological ⁴⁵Ca²⁺ uptake and radioligand binding assays. Menthol is a major constituent of peppermint oil and is approximately twice as potent as peppermint oil as an inhibitor of K⁺ depolarization-induced and electrically stimulated responses in ileum and electrically stimulated atrial and papillary muscles. IC₅₀ values in the ileal preparation ranged from 7.7 to 28.1 μg ml⁻¹ and in the cardiac preparations from 10.1 to 68.5 μg ml⁻¹. Similar potencies were demonstrated against K⁺ depolarization-induced ⁴⁵Ca²⁺ uptake in synaptosomes and against K⁺ depolarization and Bay K 8644-induced uptake in chick retinal neurons. IC₅₀ values for menthol inhibition of K⁺ and Bay K 8644 responses in the retinal neurons were 1.1 × 10⁻⁴ M (17.2 μg ml⁻¹) and 1.75 × 10⁻⁴ M (26.6 μg ml^−I), respectively, and for peppermint oil were 20.3 and 41.7 μg ml⁻¹ respectively. Both menthol and peppermint oil inhibited specific [³H]nitrendipine and [³H]PN 200–110 binding to smooth and cardiac muscle and neuronal preparations with potencies comparable to, but slightly lower than, those measured in the pharmacological and ⁴⁵Ca²⁺ uptake experiments. Binding of menthol and peppermint oil, studied at 78 μg ml⁻¹, was competitive against [³H]nitrendipine in both smooth muscle and synaptosome preparations. The data indicate that both menthol and peppermint oil exert Ca²⁺ channel blocking properties which may underlie their use in irritable bowel syndrome. Ca²⁺ channel antagonism may not be the only pharmacological effect of menthol and peppermint oil contributing to intestinal smooth muscle relaxation.