Neuropeptide‐interactions in Gastric Mucosal Defense Initiated Centrally in the Rat.

Abstract

BackgroundSeveral neuropeptides were shown to elicit gastric mucosal protective effect given centrally (intracerebroventricularly /i.c.v./, intracisternally or into discrete brain areas), e.g. TRH, opioid peptides, ghrelin, nociceptin, agmatine, substance P (SP), angiotensin II (Ang II) etc. However, numerous data suggest interactions between neuropeptides or with other endogenous mediators. Aim: To analyse if additional neuropeptides are involved in the gastroprotective effect of Ang II or agmatine (endogenous ligand of imidazoline receptors). Methods: Gastric mucosal lesion was elicited by oral administration of acidified ethanol. The compounds were given i.c.v. 10 min prior to ethanol and the lesions were determined 60 min later. The mucosal somatostatin and CGRP contents were determined by RIA. Results: 1. Both Ang II (0.012‐0.191 nmol) and agmatine (0.88‐4.4.nmol) induced significant reduction of the gastric lesions. 2. Parallel, the dramatic decrease of mucosal CGRP and somatostatin levels of gastric mucosa following ethanol administration was restored by both compounds. 3. The gastroprotective effect of Ang II was inhibited both by candesartan and L 733 060, selective NK1 receptor antagonist. Moreover, the protective effect of agmatine was inhibited both by alpha2/imidazoline I1 receptor antagonists idazoxan/efaroxan and the selective I1 receptor ligand, AGN 192403 as well as the opioid receptor antagonist, naloxone.ConclusionSP and opioid peptides might be involved in the gastroprotive effect of Ang II and agmatine, respectively.Supported by OTKA 75965