The actions of peppermint oil and menthol on calcium channel dependent processes in intestinal, neuronal and cardiac preparations.
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 micrograms ml-1 and in the cardiac preparations from 10.1 to 68.5 micrograms 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 x 10(-4) M (17.2 micrograms ml-1) and 1.75 x 10(-4) M (26.6 micrograms ml-1), respectively, and for peppermint oil were 20.3 and 41.7 micrograms 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 micrograms 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.
Hawthorn
M
M
Department of Biochemical Pharmacology, School of Pharmacy, State University of New York, Buffalo 14260.
Ferrante
J
J
Luchowski
E
E
Rutledge
A
A
Wei
X Y
XY
Triggle
D J
DJ
D000818:Animals; D015220:Calcium Channels / Q000187:drug effects*; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000187:drug effects; D008297:Male; D036142:Mentha piperita; D008610:Menthol / Q000494:pharmacology*; D009206:Myocardium / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D010938:Plant Oils / Q000494:pharmacology*; D051381:Rats
D015220:Calcium Channels; D010938:Plant Oils; D008610:Menthol; C015424:peppermint oil