Membrane-bound ATP-dependent Energy Systems, as Extra- and Intracellular Key Signals for Gastrointestinal Functions and their Regulations in the Gastrointestinal Mucosa

Title:Membrane-bound ATP-dependent Energy Systems, as Extra- and Intracellular Key Signals for Gastrointestinal Functions and their Regulations in the Gastrointestinal Mucosa

Volume: 23 Issue: 27

Author(s): Gyula Mozsik*, Imre Laszlo Szabo and Jozsef Czimmer

Affiliation:

• First Department of Medicine, Univ. of Pecs, 13, Ifjusag St., 7624 Pecs,Hungary

Keywords: Gastric mucosa, peptic ulcer disease in patients; clinical pharmacology; cytoprotection in patients; gastric mucosal biochemistry; ATP, ADP, AMP, cAMP, lactate in GI tissues; membrane-bound ATP-dependent enery systems; human peptic ulcer; energetical gradients in the human fundic, antral, duodenal and jejunal mucosa patients with different gastric acid secretion; seventeen experimental ulcer models; gastrointestinal mucosal damage and prevention vs ATP-dependent energy systems; “chemical” vs. “surgical vagotomy”; no presence of tissue hypoxia in the ulcerated GI mucosa; chemical agents and drugs to produce GI mucosal damage and its prevention; no direct damaging actions of Helicobacter pylori actions on different cellular components.

Abstract: Aims: Our research group has carried out various biochemical examinations in rat gastric ulcer models and in human gastrointestinal resecates obtained from patient who underwent gastric intervention due to peptic ulcer disease. Biochemical methods gave excellent possibility to approach the biochemical events taking place in tissues, cellular and subcellular regulatory levels during of ulcer development and of its prevetions. This paper gives a brief summary of these biochemical examinations conducted during this study period started from the 1960's up till now.

Results and Conclusions: 1. The decreased action of gastric acid secretory responses is not needed for duodenal and gastric ulcer healing in patients with peptic ulcer; 2. The surgical and chemical vagotomy resulted in various biochemical changes in the rat stomach; 3. The presence of Na+-K+-dependent ATPase and adenylate cyclase can be demostrated both in the rat and human gastric fundic mucosa; 4. The mitocondrial ATP is a common substrate for these membrane-bound ATP-dependent enzymes, and a multiple feedback mechanism existing between these two membrane-bound enzymes altered by mediators, hormones and drugs; 5. This feedback mechanism exists in the GI mucosa under different pathological conditions and during certain drug actions; 6. The development of mucosal damage and prevention depends on the actual regulatory state of above mentioned feedback mechanism between the membrane-bound ATP-dependent energy systems; 7.The drug actions depend on the actual functional state of target organ; 8. Biochemical gradients exist between the biochemical structure of the fundic, antral, duodenal and jejunal mucosa in patients with gastric hyperacidity, which is gradually downregulated by the decrease of gastric acid secretory responses, and totally disappears in patients with hypacidity; 9. No biochemically proven tissue hypoxia – around the chronic ulcer, duodenal and jejunal ulcers – exists in patients with chronic peptic ulcer; 10. The cellular and tissue protection differ from each other in the gastrointestinal tract; 11. Helicobacter pylori does not produce damage at the level of cell membrane, mitochondrion and DNA – given alone or in combination with indomethacin – on freshly isolated rat gastric mucosal cells. 12. A biochemical explanation is given to ulcer development in humans and in different animal models.

Cite this article as:

Mozsik Gyula*, Szabo Laszlo Imre and Czimmer Jozsef, Membrane-bound ATP-dependent Energy Systems, as Extra- and Intracellular Key Signals for Gastrointestinal Functions and their Regulations in the Gastrointestinal Mucosa, Current Pharmaceutical Design 2017; 23 (27) . https://dx.doi.org/10.2174/1381612823666170616080517