Centrally-Initiated Gastroprotection: Similar and Distint Mechanisms

Besides the well defined peripheral mechanisms, increasing number of evidence suggest the pivotal role of CNS in the gastric mucosal defence. Numerous neuropeptides as well as other mediators/modulators were demonstrated to initiate a chain of events following central administration, which resulted in mucosal defence. Vagal nerve is likely to play a basic role in conveying the centrally induced effect to the periphery, to gastric mucosa. Biochemical and pharmacological analysis suggest vagally mediated release of prostaglandins, nitric oxide and the release of sensory neuropeptides from capsaicin sensitive afferent nerves (1). However, besides the similarities several differences can also be observed in the gastro-protective mechanisms of different neuropeptides and other mediators. For example differences in the brain areas where the central gastroprotection can be initiated, additional pathways (e.g. sympathetic nervous system) that convey the central effect to the periphery (2), additional gastrointestinal effects (gastric acid secretion, gastric motor activity, regulation of food intake), differences in potencies, in dose-response curves, in interactions with other peptides/mediators, in effectiveness following peripheral administration and also differences can be observed in their efficacy in different ulcer models. Analysis and clarification of these additional factors may result in better understanding the complex mechanism of central regulation of gastrointestinal homeostasis.