Participation of vanilloid/capsaicin receptors, calcitonin-gene-related peptide and substance P in gastric protection of omeprazole and omeprazole-like compounds

Abstract

The effects of omeprazole and different omeprazole-like compounds, associated with anti-ischaemic, antioxidant and poly(adenosine-diphosphate-ribose) polymerase (PARP) inhibitory properties, on the gastric acid secretion (4 h pylorus-ligated) and indomethacin-induced gastric mucosal damage connected with the specific immunohistochemical distribution of TRPV1, CRGP and SP during the effects of these compounds, were studied. The observations were carried out in CFY-strain rats (180-210 g), according to the standard methods and the above-mentioned parameters were studied in these experimental circumstances without and with application of different compounds. We found that: (1) all of the compounds dose-dependently inhibited the gastric acid secretion and mucosal damage; (2) the expression of TRPV1 receptor, CGRP and SP decreased significantly in both pylorus-ligated and indomethacin-treated animals and (3) the expression of TRPV1 and CGRP was reduced. Meanwhile, no change was obtained in SP expression during the gastric mucosal protection produced by omeprazole and omeprazole-like compounds. The conclusions were that (1) a functional overlap exists between the capsaicin-sensitive afferent and efferent vagal nerve during omeprazole effects; (2) chemical modification of omeprazole molecule offers a new pathway to obtain a new drug for the introduction in the clinical practice.

Neural Cell Behavior and Fuzzy Logic

“…This second messenger works intensively for repair. So, acute enhancement of cyclic AMP (20 min) by exposure of cyclic AMP agonist produced a sensitization of rat sensory neurons and a release of immunoreactive substance P, which (such as the cyclic AMP) produces protection [668,866,364] and excites neural cells. At the same time, long-term exposure of the agonist does not appear to downregulate its ability to augment substance P release, to increase cyclic AMP production or to be sensitized [147].…”

“…Serotonin ameliorates cellular damage [1370,1107], plays a pivotal role in the homeostasis of neural tissue [69] and stimulates cell proliferation. Peptide neurotransmitter substance P also protects neurons [866,364]. Motivationally relevant substances, neuropeptides and neurohormones also affect the processes of neuronal damage, when they act on behavior 1 .…”

The Role of Capsaicin-Sensitive Afferent Nerves in Gastric Mucosal Protection Initiated Centrally or Peripherally under Experimental Conditions

“…Mozsik et al [117] suggested participation of vanilloid/capsaicin receptors, CGRP and substance P in gastric protection of omeprazole and omeprazole-like compounds.…”

Approach to Role of Capsaicin - Sensitive Afferent Nerves in the Development and Healing in Patients with Chronic Gastritis

“…In our further research significant changes were observed in the immunhistological distribution of TRPV1, CGRP and SP in patients with chronic H. pylori positive gastritis and in histological healthy subjects but no change could be detected between the patients suffered from chronic gastritis without or with H. pylori infection . The effect of omeprazole and omeprazole-like compounds could also be demonstrated in the gastric mucosa of rats by the changes of the TRPV1, CGRP and SP immunodistribution and by the reduction of number and severity of gastric mucosal lesions (Mózsik et al, 2005b).…”