calcitonin and Stomach-Ulcer

In the present study, two ulcer models--central thyrotropin-releasing hormone (TRH) injection and cold-restraint stress (CRS) application--were compared. Animals were treated either with salmon calcitonin (sCT) or saline intracerebroventricularly (ICV) before CRS exposure or ICV TRH injection. In both models, besides ultrastructural properties, ulcer indexes and lipid peroxidation (LP) and glutathione (GSH) levels of liver and stomach were determined. While TRH treatment did not affect GSH and LP levels of the stomach and led to a slight decrease in hepatic GSH levels, CRS induced a marked reduction in gastric and hepatic GSH and an increase in LP levels of both tissues. sCT pretreatment prevented the reduction of gastric and hepatic GSH levels and morphological damage of both tissues in the CRS group. However, the same treatment did not prevent the TRH-induced reduction of hepatic GSH levels and, interestingly, it worsened the ultrastructural disturbances in the liver. Although sCT prevented macroscopic ulcer formation in both models, it did not totally reverse the microscopic effects of TRH.

Topics: Animals; Calcitonin; Cold Temperature; Disease Models, Animal; Female; Gastric Mucosa; Glutathione; Injections, Intraventricular; Lipid Peroxidation; Liver; Male; Rats; Rats, Wistar; Restraint, Physical; Stomach; Stomach Ulcer; Thyrotropin-Releasing Hormone

Male young adult Wistar rats were treated parenterally with cortisol and cortisol combined with salmon calcitonin for 28 and 56 days and the stomach was investigated histologically as well as the G cells using immunohistochemistry. After 28 days of cortisol administration desquamation of the superficial layers of gastric mucosa was found and after 56 days ulcer-like changes developed and increased gastrin immunoreactivity was observed. Administration of high doses of salmon calcitonin together with cortisol resulted in a significant hypoplasia of G cells and prevented the pathological changes in the gastric mucosa.

Topics: Animals; Calcitonin; Disease Models, Animal; Drug Interactions; Gastric Mucosa; Gastrins; Hydrocortisone; Immunohistochemistry; Injections, Intraperitoneal; Male; Rats; Rats, Wistar; Stomach Ulcer

The central nervous system action of calcitonin to influence various experimental models of gastric ulcers and gastric function was studied in rats fasted for 24 h. Intracisternal injection of salmon calcitonin (5 micrograms) completely suppressed gastric ulcerations induced by exposure to cold restraint stress, intracisternal injection of a stable thyrotropin-releasing hormone analogue, or peroral administration of aspirin. By contrast, intracisternal calcitonin enhanced gastric lesions elicited by peroral administration of 40% ethanol or 0.6 N HCl. Calcitonin action was dose-dependent (0.01-1 microgram) and central nervous system mediated inasmuch as intravenous calcitonin, given at a dose 50-fold higher than that effective intracisternally, did not significantly modify gastric mucosal injuries elicited by aspirin or ethanol. Intracisternal injection of calcitonin at 0.01 microgram inhibited gastric acid output by 90% in pylorus-ligated rats and suppressed gastric emptying of a liquid meal by 63%-94% in doses ranging from 0.01 to 5 micrograms. Prostaglandin generation in the gastric mucosa was not modified by intracisternal injection of calcitonin. These results demonstrate that intracisternal calcitonin acts within the brain to potently prevent ulcer formation elicited by stress, thyrotropin-releasing hormone analogue, or aspirin, but is not cytoprotective against necrotizing agents. Calcitonin action is not related to modification of gastric prostaglandin generation but it may involve the inhibition of gastric secretory and motor function.

Topics: Animals; Brain; Calcitonin; Gastric Acid; Gastric Emptying; Gastric Mucosa; Male; Prostaglandins; Rats; Rats, Inbred Strains; Stomach Ulcer

Injection of salmon calcitonin into the lateral ventricle or the cisterna magna was reported to potently inhibit gastric lesions induced by cold restraint stress. The forebrain sites of action were investigated using unilateral microinjection of salmon calcitonin prior to exposing conscious pylorus-ligated rats to cold restraint stress for 2 hr. Calcitonin (100 ng), microinjected in 100 nl volume by pressure ejection from glass micropipette positioned into the lateral or ventromedial hypothalamus or the paraventricular nucleus, prevented the development of gastric lesions whereas microinjections into the caudate putamen, the cerebral cortex or the hippocampus were ineffective. The antiulcerogenic effect of lateral hypothalamic injection was dose dependent and specific since calcitonin gene-related peptide, tested under the same conditions, had no effect. Microinjection of calcitonin at 100 ng dose into the ventromedial hypothalamus did not modify gastric secretion whereas microinjection into the lateral hypothalamus or the paraventricular nucleus induced 75-82% inhibition of gastric acid output in pylorus-ligated rats exposed to restraint stress. These results demonstrate that the hypothalamus including the lateral, ventromedial and paraventricular nuclei are responsive sites of action for calcitonin-induced inhibition of cold restraint stress ulcers. The antiulcerogenic effect may be related to suppression of gastric acid secretion along with other mechanisms that remain to be elucidated.

Topics: Animals; Calcitonin; Cold Temperature; Dose-Response Relationship, Drug; Gastric Acid; Hypothalamus; Male; Microinjections; Rats; Rats, Inbred Strains; Restraint, Physical; Stomach Ulcer; Stress, Physiological

Many different experimental models for the induction of gastric ulcers have been reported in rats. Most of these experimental designs are often not reproducible and the interpretation of the results obtained is sometimes difficult. In the present study, three different models were found to give reliable and reproducible results, which could be repeated at any time of the year with different experimenters performing the procedure. To date, these methods are in our opinion, the best in designing gastric ulcer experiments and assessing the effect of pharmacological active substances. Two pharmacological active substances were investigated in the present study, pindolol, a beta-blocking agent with intrinsic sympathomimetic activity and salmon calcitonin, a hormone influencing calcium homeostasis in blood. Using all three different models no effect was seen after pindolol administration, while a strong inhibitory effect on the formation of gastric ulcers was observed after salmon calcitonin. Following ligation of the pylorus, the ulcer formation rate was significantly decreased from 80 to 33% with a significant fall in ulcer index from 2 to 0.42 and reduction of the ulcer areas from 6.6 to 0.58 mm2 (p less than 0.05). In addition, following phenylbutazone administration the appearance of gastric ulcers was diminished after salmon calcitonin from 1.4 to 0.43 and in ulcer area from 4.5 to 0.95 mm2 (p less than 0.01). These three ulcer models used in the present study were found to be very reliable as compared with other models reported in the literature and tested in our laboratory.

Topics: Animals; Calcitonin; Disease Models, Animal; Ligation; Male; Phenylbutazone; Pindolol; Pylorus; Rats; Stomach Ulcer; Stress, Physiological