In the last decades several neuropeptides, such as thyreotropin‐releasing hormone (TRH), amylin, neurotensin, ghrelin, melatonin, opioid peptides, substance P (SP), angiotensin II (Ang II) have been shown inhibit the gastric mucosal lesions induced by different ulcerogenic agents given centrally in the dose range of fmol to nmol. The site of action is likely to be the dorsal vagal complex. However, the different neuropeptides can interact with each other at different levels and can affect each other's biological actions. Among others nociceptin ‐ opioid; angiotensin ‐ cannabinoid, opioid; CRF ‐ beta‐endorphin, somatostatin interactions have been demonstrated. Aim of the present study was to elucidate potential interactions between neuropeptides and cannabinoids in gastric mucosal defense.MethodsGastric damage was induced by acidified ethanol in the rat (150–170 g, males); the gastric mucosal lesions were detected 60 min after ethanol administration. The dugs were given intracerebroventricularly (i.c.v.) 10 min before ethanol challenge. Gastric mucosal CGRP, somatostatin levels were determined by RIA.ResultsThe gastroprotective effect of SP, nociceptin or cannabinoids was reversed by endomorphin2‐antiserum or the opioid receptor antagonist naloxone, while the Ang II‐induced protection was decreased by the CB1 receptor antagonists, AM‐251.ConclusionNeuropeptides have prominent role in central regulation of gastric mucosal integrity. In addition, interactions between neuropeptides result in redundancy in centrally‐initiated gastric mucosal defense.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.