cyclic-gmp and Peptic-Ulcer

Bicarbonate secretion from the surface epithelial cells of the gastroduodenal mucosa is an active process depending upon the tissue metabolism and plays an important role as the first line of defense in mucosal protection in collaboration with the mucus gel. This secretion is regulated by humoral and neural factors as well as endogenous prostaglandins (PGs) and is considered to be intracellularly mediated by cyclic AMP in the duodenum and by cyclic GMP in the stomach. Ca2 also acts as an intracellular mediator in this process. This bicarbonate secretion is markedly increased in response to luminal acid, mediated by PGs and neural factors including capsaicin-sensitive sensory nerves, and the impairment of this response is involved in the pathogenesis of various duodenal ulcer models induced by cysteamine, nonsteroidal antiinflammatory drugs and stress. The mechanisms underlying the mucosal protection by HCO3 secretion is two fold; One is the direct neutralization of H + in the lumen, and the other is the establishment of a pH gradient across the mucus gel aided by the physico-chemical property of the mucus. However, the cellular mechanisms of HCO3 secretion, including the receptors, the mediators and the signal transduction pathway have been poorly understood. The establishment of a method for preparing isolated epithelial cells and the probe for HCO3 secretion in isolated cells is required to further elucidate the mechanism of HCO3 secretion.

Topics: Animals; Bicarbonates; Calcium; Cyclic AMP; Cyclic GMP; Duodenum; Gastric Mucosa; Intestinal Mucosa; Peptic Ulcer; Prostaglandins; Rats

We examined the effect of sildenafil, an inhibitor of phosphodiesterase subtype 5, that catalyzes hydrolysis of 3',5'-cyclic guanosine monophosphate (cGMP), on indomethacin-induced small-intestinal ulceration in rats and investigated the mechanism of this action, especially in relation to endogenous nitric oxide (NO). Animals without fasting were given indomethacin (10 mg/kg) s.c. and then killed 24 h later. Indomethacin produced hemorrhagic lesions in the small intestine, accompanied by a promotion of enterobacterial invasion and the expression of inducible NO synthase (iNOS) as well as myeloperoxidase (MPO) activity in the mucosa. Sildenafil (3-20 mg/kg), given p.o. 30 min before indomethacin, dose-dependently reduced the severity of these lesions, with concomitant suppression of the increase in MPO activity, iNOS expression and bacterial invasion. These effects were attenuated by the prior administration of the nonselective NOS inhibitor, N (G)-nitro-L-arginine methyl ester, in an L-arginine-reversible manner. Indomethacin also decreased the secretion of mucus and fluid (enteropooling) and enhanced intestinal motility, but these responses were all prevented by the prior administration of sildenafil. Likewise, pretreatment of the animals with NOR-3, a NO donor, also reversed the functional changes caused by indomethacin, followed by suppression of bacterial invasion and iNOS expression, and prevented the development of intestinal lesions. These results suggest that sildenafil prevents indomethacin-induced small-intestinal ulceration in rats, via a NO/cGMP-dependent mechanism, and this effect is functionally associated with an increase in the secretion of mucus/fluid and a decrease of hypermotility, resulting in the suppression of bacterial invasion and iNOS expression following indomethacin treatment.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Cyclic GMP; Enterobacteriaceae; Gastrointestinal Contents; Gastrointestinal Motility; Indomethacin; Intestinal Mucosa; Intestine, Small; Male; Mucus; Nitric Oxide; Nitric Oxide Donors; Nitric Oxide Synthase Type II; Nitro Compounds; Peptic Ulcer; Peroxidase; Phosphodiesterase 5 Inhibitors; Piperazines; Purines; Rats; Rats, Sprague-Dawley; RNA, Messenger; Sildenafil Citrate; Sulfones

Hyperbaric oxygenation (HBO) and pyridinolcarbamat were mainly applied in the treatment of elderly patients with peptic ulcer attended by coronary heart disease and atherosclerosis. To evaluate the condition of intracellular regulators after the treatment, a study was made of the time-course of changes in the content of cyclic nucleotides in blood plasma and gastric mucosa. The use of HBO in the treatment of peptic ulcer raised the efficacy of the multimodality therapy and accelerated the epithelization of erosive and ulcerative defects. The use of pyridinolcarbamat turned to produce a beneficial therapeutic effect and to be protective with respect to the gastric mucosa. Thus it was found desirable to apply the drug to the treatment of ulcers mainly occurring in the stomach. The changes in the content of cyclic nucleotides in blood plasma and gastric mucosa may play an important role in the realization of positive metabolic changes in gastric mucosa, induced by pyridinolcarbamat and HBO in peptic ulcer patients.

Topics: Aged; Anti-Ulcer Agents; Carbamates; Combined Modality Therapy; Cyclic AMP; Cyclic GMP; Female; Gastric Mucosa; Humans; Hyperbaric Oxygenation; Hypoxia; Male; Middle Aged; Peptic Ulcer; Pyridinolcarbamate

The level of cyclic nucleotides in biological material undergoes changes due to endoscopic treatment of gastric and duodenal ulcers with the help of helium-neon laser radiation which, in addition to dynamics of the clinical picture and gastroduodenoscopic data, makes it possible to diagnose the disease remission and in certain cases to predict the course of peptic ulcer.

Topics: Cyclic AMP; Cyclic GMP; Duodenum; Gastric Mucosa; Humans; Intestinal Mucosa; Lactates; Lactic Acid; Laser Therapy; Peptic Ulcer

Plasma and urine levels of cyclic adenosine 3',5'-monophosphate (cAMP) and of cyclic guanosine 3',5'-monophosphate (cGMP) were measured in 35 normal subjects, in 24 patients with nonneoplastic diseases (iron deficiency anemia, peptic ulcer, and cholelithiasis), and in 50 leukemic patients. The leukemic group included patients with acute lymphoblastic leukemia, acute myelogenous leukemia, chronic lymphocytic leukemia, and chronic myelogenous leukemia. All patients were recently diagnosed and untreated, except for 5 patients with blastic transformation of chronic myelogenous leukemia who had been previously treated. There were no significant differences in plasma and urine cyclic nucleotide levels between normal subjects and patients with nonneoplastic diseases. In leukemic patients, plasma and urine cAMP levels were similar to those of normal subjects, whereas plasma and urine cGMP levels were markedly elevated. There were no significant differences in cGMP values between the various types of leukemia. After starting treatment, plasma cyclic nucleotide levels were periodically measured in 21 of the patients with acute leukemia; cGMP levels were normalized in all the 16 subjects who attained complete remission, whereas both cAMP and cGMP levels were apparently unaffected in the patients who did not respond to treatment. This suggests that plasma or urine cGMP could be used as an additional parameter to monitor the patient's response to treatment.

Topics: Acute Disease; Adolescent; Adult; Aged; Anemia, Hypochromic; Cholelithiasis; Chronic Disease; Cyclic GMP; Female; Humans; Leukemia; Male; Middle Aged; Nucleotides, Cyclic; Peptic Ulcer

Topics: Adolescent; Adult; Aged; Anemia, Pernicious; Betazole; Cyclic AMP; Cyclic GMP; Female; Gastric Juice; Gastric Mucosa; Gastrins; Histamine; Humans; Male; Middle Aged; Pentagastrin; Peptic Ulcer; Stomach Neoplasms; Zollinger-Ellison Syndrome