Interrelationships between membrane-bound ATP-dependent energy systems, gastric mucosal damage produced by NaOH, hypertonic NaCl, HCl, and alcohol, and prostacyclin-induced gastric cytoprotection in rats.
Rat gastric mucosal lesions (ulcers) were produced by topical application of 0.2 M NaOH, 25% NaCl, 0.6 M HCl and 96% ethanol. The animals were sacrificed 1 hr after administration of the different necrotizing agents. The number of gastric lesions (ulcers) was noted and their severities scored. Different doses (5 and 50 micrograms.kg-1) of prostacyclin (PGI2) were given intraperitoneally at 30 minutes before administration of necrotizing agents, and their effects were studied on the number and severity of gastric lesions (ulcers). At the time of killing of animals, the rat gastric fundic mucosa was removed for biochemical examinations. Tissue levels of adenosine triphosphate (ATP), adenosine diphosphate (ADP), adenosine monophosphate (AMP) and lactate were determined enzymatically, while the tissue content of cyclic adenosine monophosphate (cAMP) was measured by radioimmunoassay. The values of the adenylate pool (ATP + ADP + AMP), the ratio of ATP X ADP-1 and the energy charge (ATP + 0.5 ADP X ATP + ADP + AMP-1) were calculated. All biochemical results were calculated in relation to one mg mucosal protein. It was found that:1. the tissue levels of ATP, cAMP, AMP decreased significantly, while the tissue level of ADP increased (without statistical significance) in all models, during the development of gastric mucosal damage; 2. the tissue level of lactate increased only in the model produced by 0.6 M HCl, while its level was unchanged in the other models during the development of gastric mucosal damage; 3. PGI2 decreased dose-dependently the number and severity of gastric lesions (ulcers); 4. the tissue level of ATP, ratio of ATP X ADP-1 and energy charge were decreased significantly, while the tissue level of ADP was increased significantly by PGI2 in all models; 5. the tissue level of lactate and the adenylate pool remained unchanged during the PGI2 effects. It was concluded that: 1. the development of gastric mucosal damage, produced by topical application of 0.2 M NaOH, 25% NaCl, 0.6 M HCl and 96% ethanol, is associated with an active metabolic adaptation of the gastric fundic mucosa; 2. the metabolic adaptation of the rat gastric fundic mucosa is further increased by PGI2, without resulting in hypoxaemic damage of the gastric mucosa; 3. the feed-back mechanism system - between the membrane-bound ATP-dependent energy systems - is broken during the development of gastric mucosal damage produced by different necrotizing agents, which is modified further by PGI2 at the time of gastric cytoprotection.(ABSTRACT TRUNCATED AT 400 WORDS)
D000244:Adenosine Diphosphate / Q000378:metabolism; D000249:Adenosine Monophosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism; D004734:Energy Metabolism; D011464:Epoprostenol / Q000494:pharmacology*; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism*; D008297:Male; D051381:Rats; D013276:Stomach Ulcer / Q000139:chemically induced / Q000378:metabolism* / Q000517:prevention & control
D000249:Adenosine Monophosphate; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D011464:Epoprostenol; D000242:Cyclic AMP