endomorphin-1 and Stomach-Ulcer

Several human and experimental data suggest the particular importance of gastric protective processes in maintaining mucosal integrity. Both peripheral and central mechanisms are involved in this process. In the periphery, pre-epithelial mucus-bicarbonate layer, mucus, phospholipids, trefoil peptides, prostaglandins, heat shock proteins, sensory neuropeptides, nitric oxide, and hydrogen sulfide may mediate mucosal protection. In the central nervous system hypothalamus and dorsal vagal complex (DVC) have particular important role in the regulation of centrally-induced gastroprotection. Stimulation of paraventricular nuclei either aggravates or inhibits the mucosal injury depending on the ulcer model. Vagal nerve also has a dual role, its activation can induce mucosal injury (by high dose of thyrotropin- releasing hormone (TRH), electrical stimulation), however, integrity of vagal nerve is necessary for gastroprotection induced either peripherally (by PGE2, prostacyclin, adaptive cytoprotection), or centrally (e.g. by neuropeptides). The centrally induced gastroprotection is likely to be vagal dependent, though vagal independent pathways have also been shown. Endomorphin-1 and endomorphin-2, selective μ-opioid receptor ligands, proved to be highly potent and effective gastroprotective agents in ethanol ulcer model (0.03-3 pmol intracerebroventricularly). Inhibition of the degradation of endomorphins by diprotin A resulted in gastroprotective effect, indicating the potential role of these endogenous opioids in the regulation of gastric mucosal integrity. Endomorphin-2 injected intracerebroventricularly restored the reduced levels of CGRP and somatostatin in gastric mucosa induced by ethanol. In conclusion, neuropeptides expressed in dorsal vagal complex and hypothalamus may have a regulatory role in maintaining gastric mucosal integrity by stimulating the formation of mucosal protective compounds.

Topics: Animals; Calcitonin Gene-Related Peptide; Central Nervous System; Ethanol; Gastric Mucosa; Humans; Hypothalamus; Neuropeptides; Oligopeptides; Opioid Peptides; Stomach Ulcer

Beta-endorphin, deltorphin II, [D-Ala2, Phe4, Gly5-ol-enkephalin (DAGO) as well as endomorphin-1 and endomorphin-2 injected intracerebroventricularly (i.c.v.) induced gastroprotective action. It has been raised that endogenous opioids may have a central role in maintaining gastric mucosal integrity. Therefore we aimed to study the role of endogenous opioid system in the gastroprotective action induced by activation of alpha 2-adrenoceptors, nociceptin- and cannabinoid-receptors. Our results suggest that the non-selective opioid receptor antagonist naloxone (27 nmol i.c.v.) and the delta-opioid receptor antagonist naltrindole (5 nmol i.c.v.) abolished the mucosal protective effect of alpha 2-adrenoceptor agonists clonidine (470 pmol i.c.v.) and rilmenidine (45 pmol i.c.v.), nociceptin (1 nmol i.c.v.) and the cannabinoid receptor agonist anandamide (110 nmol i.c.v.). Based on our findings it can be raised that opioid system besides its well known regulatory functions might be involved in maintenance of gastric mucosal integrity.

Topics: Animals; Arachidonic Acids; beta-Endorphin; Clonidine; Endocannabinoids; Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; Ethanol; Excitatory Amino Acids; Gastric Mucosa; Injections, Intraventricular; Male; Naloxone; Naltrexone; Narcotic Antagonists; Neurotransmitter Agents; Nociceptin; Oligopeptides; Opioid Peptides; Oxazoles; Polyunsaturated Alkamides; Rats; Rats, Wistar; Receptors, Opioid; Rilmenidine; Stomach Ulcer