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

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 Ba 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.

Relaxant Effect of Monoterpene (−)-Carveol on Isolated Human Umbilical Cord Arteries and the Involvement of Ion Channels

“…Similar to our results, several monoterpenes have been suggested to block VOCCs in smooth muscles from various rat organs; these include citral in the aorta [31], 1,8-cineole, citral and limonene in the trachea [42,43], as well as citral and limonene in the uterus [44]. In addition, endogenous substances, such as progesterone and 5β-pregnanediol, have shown that VOCC inhibition is the main vascular relaxation route stimulated by these hormones in HUA vessels [33].…”

Antispasmodic effects of the essential oil of Croton zehnteneri, anethole, and estragole, on tracheal smooth muscle

“…The major mechanism of the electromechanical coupling is the increase in Ca 2þ inflow to the intracellular compartment through VDCC [30,36]. Blockade of activation of L type VDCC is able to completely block the 60 mM K þ -induced contraction of the trachealis muscle, as demonstrated by others [27,30,37] and the present work with the action of nifedipine (Figure 3B).…”

“…Tissue preparation and isometric tension recording procedures were performed as previously described [30]. After animal sacrifice, the trachea was dissected and connective tissues were removed.…”

“…Dissociation of tracheal smooth muscle and ionic current recording were performed as previously described [30]. The trachea was immediately dissected, attached tissues and cartilage removed, and placed in a physiological saline solution (PSS) containing low concentration of Ca 2þ (PSS-Ca 2þ 0.05 mM).…”

“…These include OVA-induced increase in Newtonian resistance, which represents resistance of respiratory conduits to air flow, plus increase of oxidative stress and of inflammatory cells in the pulmonary parenchyma [24]. Our research group has shown that antispasmodic action appears to be a common pharmacological effect of various essential oils and their constituents on the smooth musculature of various systems [22,25,26,27,28,29,30]. Accordingly, we hypothesized that this decrease in Newtonian resistance could be due to antispasmodic effect, and probably an anti-inflammatory activity.…”