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

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.

Immunohistochemical distribution of vanilloid receptor, calcitonin-gene related peptide and substance P in gastrointestinal mucosa of patients with different gastrointestinal disorders.

The immunohistochemical distribution of capsaicin/vanilloid (transient receptor potential vanilloid 1, TRPV1) receptors and neuropeptides (CGRP, SP) was studied in the gastrointestinal mucosal biopsies of patients with gastritis, erosions, ulcers, polyps, adenocarcinoma, chronic inflammatory bowel diseases, polyps without and with hyperplasia, dysplasia and adenocarcinoma in colon. The studies were carried out in 127 patients and 30 people with only functional dyspepsia (without any histological alteration). The results were: (1) the positivity of TRPV1 receptor and CGRP was detected, and weak participation of SP was detected in patients with different gastric diseases; (2) the presence of TRPV1, CGRP and SP could be detected in chronic inflammation of bowel disease; (3) SP could not detected in patients with colon polyps, dysplasia and adenocarcinoma; (4) the presence of TRPV1 and CGRP was proved in colon dysplasia and adenocarcinoma. We conclude that (1) the immunohistochemical distribution of TRPV1, CGRP and SP differs in gastrointestinal diseases of the upper and lower tract, and (2) the participation of TRPV1, CGRP and SP differs significantly in these different gastrointestinal diseases.