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A1220 - Eugenol Relaxes Isolated Airway Smooth Muscle Cells Via Calcium Signaling
Author Block: J. Huang1, R. A. Panettieri2, S. B. Liggett3, S. S. An1; 1Environmental Health Sciences, Johns Hopkins University, Baltimore, MD, United States, 2Institute for Translational Medicine and Science, Rutgers University, New Brunswick, NJ, United States, 3Personalized Medicine and Genomicx, University of South Florida Morsani College of Medicine, Tampa, FL, United States.
Rationale: Eugenol, a monoterpene found in essential oils, has been shown to have diverse effects, including anti-microbial, antioxidant, anti-inflammatory and antispasmodic properties. However, the mechanistic action of eugenol on airway smooth muscle (ASM) - the end-effector cell of acute airway narrowing in asthma - is not known. Here we studied the effects of eugenol in ASM physiology and the role for OR5D16, a human ortholog of mouse eugenol odorant receptor (mOR-EG).
Methods: We used qPCR to detect the expression of mOR-EG and OR5D16 in primary ASM cells isolated from C57BL/6 mice and human lung donors. We used Fura-2 fluorescence and magnetic twisting cytometry (MTC) to measure dynamic changes in intracellular Ca2+ [Ca2+]i and single-cell contractility in response to increasing doses of eugenol. These studies were performed in the presence or absence of mOR-EG antagonists, isosafrol (ISF) and methyl isoeugenol (MIEG).
Results: mOR-EG and OR5D16 were expressed in mouse and human ASM cells. In both mouse and human ASM cells, eugenol evoked [Ca2+]i and caused relaxation in a dose-dependent manner. Eugenol-induced increases in [Ca2+]i and single-cell relaxation were markedly attenuated by ISF but not by MIEG.
Conclusions: We showed that eugenol, a monoterpene derived from clove essential oil, increases [Ca2+]i and relaxes isolated ASM cells. Eugenol-induced ASM physiology was inhibited by ISF, but not by MIEG. Interestingly, MIEG alone caused a moderate ASM relaxation while augmenting the relaxation effects of eugenol. Further loss-of-function and recovery-of-function studies are warranted to assess the potential applicability of eugenol and structurally similar monoterpenes for the treatment of obstructive lung disease.