Z Gastroenterol 2007; 45 - A3
DOI: 10.1055/s-2007-982633

Endogenous opioids may mediate the centrally-induced gastroprotective action of nociceptin and nocistatin

G Aricó 3, Z Zádori 1, N Shujaa 1, K Tekes 2, K Gyires 1
  • 1Dept. of Pharmacology and Pharmacotherapy, Faculty of Medicine, Semmelweis University, Budapest, Hungary
  • 2Dept. of Pharmacodynamics, Faculty of Pharmacy, Semmelweis University, Budapest, Hungary
  • 3Dept. of Pharmaceutical Sciences – Pharmacology Section, Faculty of Pharmacy, University of Catania, Italy

Background: Nociceptin/Orphanin FQ (Noc) and Nocistatin (NS) are two neuropeptides derived from the same precursor protein, pre-pro-Nociceptin (Okuda-Ashitaka and Seiji, 2000). Noc is considered to be the endogenous ligand of the NOP receptor, which exhibits marked structural analogy with the other classic opioid receptors. However, Noc lacks the N-terminal tyrosine necessary for the activation of the opioid receptors, and its effects are usually not reversed by naloxone. Central and peripheral administration of the Noc has been reported to exert multiple effects in the gastrointestinal (GI) tract, for example it has been shown that Noc protects against gastric mucosal damage induced by ethanol (Morini et al., 2002), stimulates gastric acid secretion (Ishihara et al., 2002) and modulates gastrointestinal propulsive activity in the rat (Broccardo et al., 2004). However, data in the literature on the antagonist effect of naloxone on Noc-induced GI actions are contradictory.

Aims: 1. To compare the gastroprotective effects of Noc and NS. 2. To analyse whether an opioid component is involved in their gastroprotective effect. Methods: Gastric mucosal damage was induced by acidified absolute ethanol in rats. The compounds were given intracerebroventricularly (i.c.v.). Results: Both Noc and NS induced gastroprotective effect in the doses of 2µg/rat i.c.v. However, higher doses (10µg/rat i.c.v.) failed to reduce the ethanol-induced mucosal lesions in a significant manner. The effect of both neuropeptides was reduced by naloxone (10µg/rat i.c.v.), the delta-opioid receptor antagonist naltrindole (2.2µg/rat i.c.v.) and the kappa-opioid receptor antagonist norbinaltorphimine (10µg/rat i.c.v.).

Conclusion: Both Noc and NS initiate centrally a series of events which result in gastric mucosal defense. The gastroprotective effect of Noc and NS was naloxone-sensitive, and both delta and kappa-opioid receptors may be involved in the action. The work was supported by ETT Grant 529