Advertisement

The mechanism of action of peppermint oil on gastrointestinal smooth muscle

An analysis using patch clamp electrophysiology and isolated tissue pharmacology in rabbit and guinea pig
  • Judith M. Hills
    Correspondence
    Address requests for reprints to: Judith M. Hills, Ph.D., Smith Kline Beecham Pharmaceuticals Ltd., The Frythe, Welwyn, Herts, AL6 9AR, England.
    Affiliations
    Smith Kline Beecham Pharmaceuticals Ltd., Welwyn, Herts, England

    Department of Pharmacology, United Medical and Dental Schools, St. Thomas' Campus, London, England
    Search for articles by this author
  • Philip I. Aaronson
    Affiliations
    Smith Kline Beecham Pharmaceuticals Ltd., Welwyn, Herts, England

    Department of Pharmacology, United Medical and Dental Schools, St. Thomas' Campus, London, England
    Search for articles by this author
      This paper is only available as a PDF. To read, Please Download here.

      Abstract

      An investigation of the mechanism of peppermint oil action was performed using isolated pharmacological preparations from guinea pig large intestine and patch clamp electrophysiology techniques on rabbit jejunum. Peppermint oil relaxed carbachol-contracted guinea pig taenia coli (IC50, 22.1 μg/mL) and inhibited spontaneous activity in the guinea pig colon (IC50, 25.9 μg/mL) and rabbit jejunum (IC50, 15.2 μg/mL). Peppermint oil markedly attenuated contractile responses in the guinea pig taenia coli to acetylcholine, histamine, 5-hydroxytryptamine, and substance P. Peppermint oil reduced contractions evoked by potassium depolarization and calcium contractions evoked in depolarizing Krebs solutions in taenia coli. Potential-dependent calcium currents recorded using the whole cell clamp configuration in rabbit jejunum smooth muscle cells were inhibited by peppermint oil in a concentration-dependent manner. Peppermint oil both reduced peak current amplitude and increased the rate of current decay. The effect of peppermint oil resembled that of the dihydropyridine calcium antagonists. It is concluded that peppermint oil relaxes gastrointestinal smooth muscle by reducing calcium influx.

      Abbreviations:

      5-HT (5-hydroxytryptamine), ACh (acetylcholine), DHP (dihydropyridine), EC (enterochromaffin), TTX (tetrodotoxin)

      References

        • Rees WDW
        • Evans BK
        • Rhodes J
        Treating irritable bowel syndrome with peppermint oil.
        Br Med J. 1979; 2: 835-836
        • Somerville KW
        • Richmond CR
        • Bell GD
        Delayed release peppermint oil capsules (Colpermin) for the spastic colon syndrome: a pharmacokinetic study.
        Br J Clin Pharmacol. 1984; 18: 638-640
        • Dew MJ
        • Evans BK
        • Rhodes J
        Peppermint oil for the irritable bowel: a multicentre trial.
        Br J Clin Pract. 1984; 38: 397-398
        • Humphrey AM
        • Goodhead K
        • Greaves JH
        • Matthew WS
        • Moyler DA
        • Perry RG
        • Ridlington J
        • Stock RA
        • Watson G
        Application of gas-liquid chromatography to the analysis of essential oils.
        Determination of limonene and 1,8-cineole in oils of peppermint. 1978; 103 (Part VI): 375-381
        • Sang JP
        Estimation of menthone, menthofuran, menthylacetate and menthol in peppermint oil by capillary gas chromatography.
        J Chromatog. 1982; 253: 109-112
        • Hills JM
        • Potts HJ
        • Carlin BA
        • Parsons ME
        An examination of the contribution made by the constituents of peppermint oil (PO) to the relaxation of gastrointestinal smooth muscle.
        Br J Pharmacol. 1990; 101: 600P
        • Taylor BA
        • Luscombe DK
        • Duthie HL
        Inhibitory effect of peppermint oil on gastrointestinal smooth muscle (abstr).
        Gut. 1983; 24: A992
        • Taylor BA
        • Luscombe DK
        • Duthie HL
        Inhibitory effect of peppermint oil and menthol on human isolated coli.
        Gut. 1984; 25: A1168-A1169
        • Duthie HL
        The effect of peppermint oil on colonic motility in man.
        Surg Res Soc Abstracts. 1981; 68: 820
        • Leicester RJ
        • Hunt RH
        Peppermint oil to reduce colonic spasm during endoscopy.
        Lancet. 1982; 2: 989
        • Rogers J
        • Tay HH
        • Misiewicz JJ
        Peppermint oil.
        Lancet. 1988; 2: 98-99
        • Hawthorne M
        • Ferrante J
        • Luchowski E
        • Rutledge A
        • Wei X
        • Triggle DJ
        Menthol and peppermint oil actions on calcium channel dependent processes in cardiac, intestinal and neuronal preparations.
        Aliment Pharmacol Therap. 1988; 2: 101-118
        • Swandulla D
        • Carbone E
        • Schafer K
        • Lux HD
        Effect of menthol on two types of Ca currents in cultured sensory neurones of vertebrates.
        Pflugers Arch. 1987; 409: 52-59
        • Benham CD
        • Bolton TB
        Spontaneous transient outward currents in single visceral and vascular smooth muscle cells of the rabbit.
        J Physiol. 1986; 381: 385-406
        • Bolton TB
        • Aaronson PI
        • Mackenzie I
        Voltage-dependent calcium channel in intestinal and vascular smooth muscle cells.
        in: Vanhouette R Paoletti R Govoni S Calcium antagonists: pharmacology and clinical research. New York Academy of Sciences, New York1988: 32-42
        • Aaronson PI
        • Bolton TB
        • Lang RJ
        • Mackenzie I
        Calcium currents in single isolated smooth muscle cells from the rabbit ear artery in normal-calcium and high-barium solutions.
        J Physiol. 1988; 405: 57-75
        • Arunlakshana O
        • Schild HO
        Some quantitative uses of drug antagonists.
        Br J Pharmacol Chemother. 1959; 14: 45-58
        • Bean BP
        • Sturek M
        • Puga A
        • Hermsmeyer K
        Calcium channels in muscle cells isolated from rat mesenteric arteries: modulation by dihydropyridine drugs.
        Circ Res. 1986; 59: 220-235
        • Campbell D
        • Giles WR
        • Hume JR
        • Shibata EF
        Inactivation of calcium current in bullfrog atrial myocytes.
        J Physiol. 1988; 403: 287-315
        • Bean BP
        Nitrendipine block of cardiac calcium channels: high affinity binding to the inactivated state.
        in: 2nd ed. Proc Natl Acad Sci USA. 81. 1984: 6388-6392
        • Schneider MME
        • Otten MH
        Efficacy of Colpermin in the treatment of patients with the irritable bowel syndrome (abstr).
        Gastroenterology. 1990; 98: A389
        • Bolton TB
        Mechanisms of action of transmitters and other substances on smooth muscle.
        Physiol Rev. 1979; 59: 606-718
        • Casteels R
        • Raeymakers L
        The action of aceycholine and catecholamines on an intracellular calcium store in the smooth muscle cells of the guinea-pig taenia coli.
        J Physiol. 1979; 294: 51-68
        • Furness JB
        • Costa M
        Neurons with 5-HT like immunoreactivity in the enteric nervous system: their projections in the guinea-pig small intestine.
        Neuroscience. 1982; 7: 341-349
        • Wood JD
        • Mayer CJ
        Slow synaptic excitation mediated by serotonin in Auerbachs plexus.
        Nature. 1978; 276: 836-837
        • Bornstein JC
        • North RA
        • Costa M
        • Furness JB
        Excitatory synaptic potentials due to activation of neurons with short projections in the myenteric plexus.
        Neuroscience. 1984; 11: 723-731
        • Buchheit KH
        • Engel G
        • Mutschler Richardson B
        Study of the contractile effect of 5-hydroxtryptamine (5-HT) in the isolated longitudinal muscle strip from the guinea pig ileum.
        Naunyn Schmiedebergs Arch Pharmacol. 1985; 329: 36-41
        • Solcia E
        • Capella C
        • Buffa R
        • Usellini L
        • Tenti P
        Ultrastructure and histochemistry of endocrine-paracrine cells in the gut.
        in: Bertaccini G Mediators and drugs in gastrointestinal motility 1. Springer-Verlag, New York1982: 55-78
        • Solcia E
        • Capella C
        • Buffa R
        • Ussellini L
        • Fiocca R
        • Frigerio B
        • Tenti P
        • Sessa F
        The diffuse endocrine-paracrine system of the gut in health and disease: ultrastructural features.
        Scand J Gastroenterol. 1981; 16: 25-36
        • Bertaccini G
        Amines: histamine.
        in: Bertaccini G Mediators and drugs in gastrointestinal motility. 2nd ed. Springer-Verlag, New York1982: 201-218
        • Bulbring E
        Changes in configuration of spontaneously discharged spike-potentials, from smooth muscle of the guinea-pigs' taenia coli. The effects of electrotonic currents and of adrenaline, acetylcholine and histamine.
        J Physiol (Lond). 1957; 135: 412-425
        • Morel N
        • Hardy J
        • Godfraind T
        Histamine-operated calcium channels in intestinal smooth muscle of the guinea pig.
        Eur J Pharmacol. 1987; 135: 69-75
        • Pearce AGE
        • Polak JM
        Immunocytochemical localization of substance P in mammalian intestine.
        Histochemistry. 1975; 41: 373-375
        • Benham CD
        • Bolton TB
        Comparison of the excitatory actions of substance P, carbachol, histamine and prostaglandin F2on the smooth muscle of the taenia of the guinea-pig caecum.
        Br J Pharmacol. 1983; 80: 409-420
        • Costa M
        • Furness JB
        • Pullin CO
        • Bornstein J
        Substance P enteric neurons mediate non-cholinergic transmission to the circular muscle of the guinea-pig intestine.
        Naunyn Schmiede-berg's Arch Pharmacol. 1985; 328: 446-453
        • Swandulla D
        • Schafer K
        • Lux HD
        Calcium channel current inactivation is selectively modulated by menthol.
        Neurosci Lett. 1986; 68: 23-28
        • Swandulla D
        • Carbone E
        • Schafer K
        • Lux HD
        Effect of menthol on two types of Ca currents in cultured sensory neurons of vertebrates.
        Pflugers Arch. 1987; 409: 52-59
        • Okabe K
        • Terada K
        • Kitamura K
        • Kuriyama H
        Selective and long-lasting inhibitory actions of the dihydropyridine derivative, CV-4093, on calcium currents in smooth muscle cells of the rabbit pulmonary artery.
        J Pharm Exp Ther. 1987; 243: 703-710
        • Yatani A
        • Seidel CL
        • Allen J
        • Brown AM
        Whole-cell and single-channel currents of isolated smooth muscle cells from saphenous vein.
        Circ Res. 1987; 60: 523-533
        • Chin JH
        Differential sensitivity of calcium channels to dihydropyridines: the modulated receptor hypothesis.
        Biochem Pharmacol. 1986; 35: 4115-4120