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1,8-Cineole blocks voltage-gated L-type calcium channels in tracheal smooth muscle

  • Muscle physiology
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Abstract

1,8-Cineole is a cyclic monoterpenoid used in folk medicine for treatment of numerous respiratory diseases and other infections. 1,8-Cineole has anti-inflammatory, antioxidant, and myorelaxant effects, as well as low toxicity. In the present study, the effects of 1,8-cineole on contractility and voltage-gated calcium channels (VGCC) in tracheal smooth muscle were investigated. Intact and dissociated tracheal smooth muscle were used for muscle contraction and patch-clamp recordings, respectively. In experiments involving muscle contraction, 1,8-cineole potentiated contractions at low concentrations and relaxed contractions induced by isotonic K+ at high concentrations. AMTB (a TRPM8 channel blocker) reduced the potentiation induced by 1,8-cineole while indomethacin (a COX inhibitor) did not block this effect. In dissociated myocytes, 1,8-cineole partially blocked Ba2+ currents through VGCC in a concentration-dependent manner. 1,8-Cineole shifted the steady-state activation and inactivation curves to the left and also reduced the current decay time constant. In conclusion, 1,8-cineole has a dual effect on tracheal smooth muscle contraction resulting in a biphasic effect. Our data suggest that the potentiation effect is mediated by activation of TRPM8 channels and the relaxation effect is mediated by the blockage of L-type VGCC.

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Acknowledgments

The authors would like to thank Mr. Pedro Militão de Albuquerque-Neto for the technical support and Dr. Daniel Weinreich for reviewing this manuscript. This work was supported by Fundação Cearense de Apoio ao Desenvolvimento Científico e Tecnológico (FUNCAP), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), and Universidade Estadual do Ceará (UECE).

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Correspondence to José Henrique Leal-Cardoso.

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All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. The study was ethically approved by the research ethics committee at the Universidade Estadual do Ceará, Brazil.

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Pereira-Gonçalves, Á., Ferreira-da-Silva, F.W., de Holanda-Angelin-Alves, C.M. et al. 1,8-Cineole blocks voltage-gated L-type calcium channels in tracheal smooth muscle. Pflugers Arch - Eur J Physiol 470, 1803–1813 (2018). https://doi.org/10.1007/s00424-018-2201-5

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