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Neuropeptides given centrally are potent gastroprotective agents.Their gastroprotective dose ranges differ significantly.Additional peripheral effects may modify their protective action.Several peptides possess bell-shaped dose–response relationship.The centrally induced gastroprotective effect of neuropeptides has been intensively studied. Besides many similarities, however, differences can also be observed in their gastroprotective actions. The gastroprotective dose–response curve proved to be either sigmoid, or bell-shaped. Additional gastrointestinal effects of neuropeptides can contribute to their mucosal protective effect. Part of the neuropeptides induces gastroprotection by peripheral administration as well. Besides vagal nerve the sympathetic nervous system may also be involved in conveying the central effect to the periphery. Better understanding of the complex mechanism of the maintenance of gastric mucosal integrity may result in the development of new strategy to enhance gastric mucosal resistance against injury.