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.
Mózsik
Gyula
G
First Department of Medicine, Medical and Health Centre, University of Pécs, H-7643 Pécs, Hungary. gyula.mozsik@aok.pte.hu
Peidl
Zsanett
Z
Szolcsányi
János
J
Dömötör
András
A
Hideg
Kálmán
K
Szekeres
György
G
Karádi
Oszkár
O
Hunyady
Béla
B
D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005750:Gastric Juice / Q000378:metabolism; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007150:Immunohistochemistry / Q000379:methods; D007213:Indomethacin / Q000008:administration & dosage / Q000633:toxicity; D007279:Injections, Subcutaneous; D009853:Omeprazole / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D011506:Proteins / Q000378:metabolism*; D011708:Pylorus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051381:Rats; D013329:Structure-Activity Relationship; D013373:Substance P / Q000378:metabolism / Q000502:physiology; D050916:TRPV Cation Channels / Q000378:metabolism
D000975:Antioxidants; D011506:Proteins; D050916:TRPV Cation Channels; D013373:Substance P; D015740:Calcitonin Gene-Related Peptide; D009853:Omeprazole; D007213:Indomethacin