From mucosal energy metabolism to capsaicin -strategies for understanding mucosal protection

Imre L. Szabó, Jozsef Czimmer, Gyula Mózsik

Research output: Chapter in Book/Report/Conference proceedingChapter

1 Citation (Scopus)

Abstract

Backgrounds: The early results of clinical pharmacological studies proved that duodenal protection existed without any decrease of gastric acid secretion (1965), and the ulcer healing rates by atropine, cimetidine and carbenoxolone (having no inhibitory effect of gastric acid secretion) were superior to that of placebo; however, no significant difference was obtained among the actions of atropine, cimetidine and carbenoxolone (1979) in patients with classic duodenal ulcer. This phenomenon observed in animal experiments was named as 'gastric cytoprotection' by André Robert in 1979. Misunderstanding the results of clinical pharmacological studies led us to start the biochemical pharmacological studies. Mucosal energy metabolism and capsaicin action were analyzed in detail by the simultaneously carried out measurements of membrane-bound ATP-dependent enzymes (membrane ATPase, adenylate cyclase), tissue levels of adenosine triphosphate (ATP), adenosine diphosphate (ADP), adenosine monophosphate (AMP), cyclic adenosine monophosphate (cAMP), RNA, DNA and lactate of GI mucosa in animal models and patients with peptic ulcers under different physiological and pathological circumstances without and with application of various drugs or compounds and surgical vagotomy. On the other hand, the possible role(s) of capsaicinsensitive afferent fibers of the vagal nerve have also been studied under various experimental conditions in animals, later in patients with different gastrointestinal disorders (peptic ulcer, chemical-induced gastric mucosal damage, chronic gastritis, ulcer, inflammatory bowel diseases) and cancers. Results: (1) Similar changes in ATP-ADP transformation (increase) and in ATP-cAMP transformation (decrease) are present in the gastric mucosa during the development of mucosal damage produced by various chemical agents in animal model experiments. (2) Drugs or other compounds (like retinoids) prevent these chemical-induced mucosal damages; however, biochemically they act on different pathways (atropine vs. cimetidine). (3) Many changes in the cellular biochemical events (mucosal energy systems, oxydative phosphorylation, RNA synthesis) are involved in both the development of mucosal damage and protection of gastric mucosa obtained by animal experiments. (4) An energetic gradient exists in the gastric fundic, antral, duodenal and jejunal mucosa in patients with peptic ulcer diseases based on their gastric basal (BAO) and maximal (MAO) acid outputs. (5) No impaired hypoxemic damage (impaired oxidative phosphorylation) could be detected in the mucosal tissue around the ulcer in patients with antral, duodenal and jejunal ulcers. (6) The existence of a very complex feedback system regulated extracellularly (drugs or other metabolites, hormones, mediators) and intracellularly (cAMP, AMP) can be proved in the GI mucosa under normal and various circumstances of mucosal damage in animals and humans (like the mechanism between the active transport system and second-messenger system). (7) The capsaicinsensitive afferent fibers of vagal nerve (in excitatory phase) represent a general mucosal defense mechanism against various noxious agents in animals and healthy human beings and patients, but capsaicin in high dose aggravates the mucosal damage. (8) The capsaicin-sensitive afferentationinduced mucosal defense seems to be independent from the success of classical eradication treatment in patients with chronic gastritis. We can conclude that the detailed studies offer new perspectives to understand the biochemical, physiological and pharmacological mechanisms involved in the mucosal damage and protection in animals and humans.

Original languageEnglish
Title of host publicationCell/Tissue Injury and Cytoprotection/Organoprotection in the Gastrointestinal Tract
Subtitle of host publicationMechanisms, Prevention and Treatment
PublisherS. Karger AG
Pages230-241
Number of pages12
Volume30
ISBN (Electronic)9783318021844
ISBN (Print)9783318021837
DOIs
Publication statusPublished - Jun 22 2012

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

Fingerprint Dive into the research topics of 'From mucosal energy metabolism to capsaicin -strategies for understanding mucosal protection'. Together they form a unique fingerprint.

  • Cite this

    Szabó, I. L., Czimmer, J., & Mózsik, G. (2012). From mucosal energy metabolism to capsaicin -strategies for understanding mucosal protection. In Cell/Tissue Injury and Cytoprotection/Organoprotection in the Gastrointestinal Tract: Mechanisms, Prevention and Treatment (Vol. 30, pp. 230-241). S. Karger AG. https://doi.org/10.1159/000338463