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Animal models of asthma have shown that limonene (terpene in citrus fruits) reduces inflammation and airway reactivity. However, the mechanism of these effects is unknown. We hypothesized that limonene activates A_2A adenosine receptors (A_2AAR) to produce its effects in asthma, after comparing Glide scores for limonene (−5.19) and A_2AAR agonist CGS 21680 (−8.43). We investigated the effects of limonene on lung inflammation and airway responsiveness to methacholine (MCh) as well NECA (nonselective adenosine analog) in A_2AAR knock‐out (A_2AKO) and wild‐type (WT) mice. Mice were divided into control (CON) and allergen sensitized‐challenged (SEN) groups, and were sensitized i.p. on days 1, 6 with 20 μg ovalbumin (OVA) followed by 5% OVA aerosol challenges on days 11–13 (n=6 mice per group). Limonene was administered as an inhalation prior to allergen challenges in one group of …