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Natural or synthetic small molecules (< 500 Da), bioactive at very low concentrations, can potentially increase plant tolerance and resilience to abiotic stresses and improve the resources use efficiency (RUE) of a wide range of crops. Hence, they represent a promising tool in coping with the increasing global food demand imposed by climate change. In this study, the responses of butterhead lettuce (cv. Trocadero) treated with omeprazole (OMP), a benzimidazole inhibitor of animal proton pumps, were studied. OMP was applied as substrate drench at five rates (0, 10, 50, 100 or 200 mu M) on lettuce plants grown under nonsaline or saline conditions of 1 or 30 mM NaCl. Increasing NaCl concentration decreased lettuce fresh and dry biomass by 37% and 25% in the 0 M OMP treatment, respectively; whereas these reductions Were mitigated by the 10 mu M (12% and 19%, respectively) and 50 mu M (15% and 14%, respectively) OMP application. Though OMP was not directly involved in ion homeostasis and K+/Na+ ratio regulation, treatment with 10 mu M OMP under saline conditions decreased Na+ in leaves and Cl- in leaves and roots while increasing NO3- concentration in both organs. The synthesis of nitrogenous osmolytes may be implicated in increasing salt tolerance and the sustenance of transpiration and photosynthesis. Under nonsaline conditions, OMP increased root biomass, improving nutrient and water uptake, and therefore RUE.