ABSTRACT
A series of 3-arylprop-2-enthionoester derivatives was synthesized. These compounds were evaluated for their antiulcer activity. Derivatives [(H), (V), (VIII)] showed a noteworthy activity.
Subject(s)
Acrylates/chemical synthesis , Anti-Ulcer Agents/chemical synthesis , Thiones/chemical synthesis , Acrylates/pharmacology , Animals , Anti-Ulcer Agents/pharmacology , Chemical Phenomena , Chemistry , Male , Rats , Rats, Inbred Strains , Stomach Ulcer/chemically induced , Thiones/pharmacologyABSTRACT
Chronic hyperprolactinemia was obtained in the rat by an implantation of two adenohypophyses under the kidney capsule. This experimental model was set to evaluate the influence that high prolactin levels may have on bone mineralization when an intervention of estrogens can reasonably be excluded. Bone density was measured by single photon absorptiometry at the femur level. Our results indicate that the increase in PRL throughout the period of observation was associated with a significant decrease in bone mineral content, while calcium and parathyroid hormone serum levels remained unchanged. This would suggest that PRL plays a role in bone calcium metabolism, that might be included among the effects of this hormone.
Subject(s)
Bone and Bones/analysis , Hyperprolactinemia/metabolism , Minerals/analysis , Animals , Bone and Bones/diagnostic imaging , Femur/diagnostic imaging , Male , Prolactin/analysis , Radionuclide Imaging , Rats , Rats, Inbred StrainsABSTRACT
The effects of different doses of Asu(1,7) eel-calcitonin, peripherally injected, on gastric secretion were studied in conscious Brattleboro rats, which are genetically deficient in vasopressin. Moreover, we evaluated the activity of this analogue on gastric ulcer formation by restraint stress. We found that 5 IU/kg Asu(1,7) eel-calcitonin decreased gastric secretion and inhibited the development of stress-induced ulcers in Brattleboro rats. These data suggest that vasopressin does not play a role in the gastrointestinal activity of Asu(1,7) eel-calcitonin.
Subject(s)
Calcitonin/analogs & derivatives , Gastric Mucosa/metabolism , Stomach Ulcer/prevention & control , Stress, Physiological/complications , Vasopressins/deficiency , Animals , Calcitonin/therapeutic use , Eels , Heterozygote , Homozygote , Injections, Intravenous , Male , Rats , Rats, Brattleboro , Reference Values , Stomach Ulcer/etiologyABSTRACT
The effects of different doses of (Asu1,7) eel-calcitonin, iv injected, on gastric secretion were studied in conscious rats with pyloric occlusion. Moreover, we evaluated the activity of this analogue on gastric ulcer formation by restraint stress. It was found that 2.5 or 5 Ul/kg (Asu1,7) eel-calcitonin decreased gastric acid secretion and inhibited the development of stress-induced ulcers in rats. In the isolated rat stomach the peptide at the concentrations of 1 nM to 1 microM did not modify acetylcholine, histamine or 5-hydroxytriptamine-induced contractions. These results suggest that this peripheral activity of (Asu1,7) eel-calcitonin does not involve a direct interference with cholinergic, histaminergic or serotonergic pathways at gastric level.
Subject(s)
Calcitonin/analogs & derivatives , Stomach/drug effects , Stress, Physiological/physiopathology , Animals , Calcitonin/pharmacology , Gastric Acid/metabolism , Gastric Juice/metabolism , In Vitro Techniques , Male , Muscle Contraction/drug effects , Muscle, Smooth/drug effects , Rats , Rats, Inbred Strains , Restraint, Physical , Stomach Ulcer/etiology , Stomach Ulcer/prevention & controlABSTRACT
Hyperprolactinaemia, as induced by pituitary homografts under the kidney capsule, was accompanied by an inhibition of development of gastric ulcers following the application of cold-plus-restraint stress in male rats. This effect was mimicked by intracisternal administration of a low dose of the hormone. Peripheral injection of the dopamine receptor antagonist, domperidone, also inhibited the development of stress-induced ulcers. However, no effect was found after peripheral injection of another dopamine receptor antagonist, haloperidol. This latter drug appeared to antagonize the cytoprotective effect of prolactin (PRL) on stress-induced ulcers. Furthermore, peripheral injection of the prostaglandin synthesis inhibitor, indomethacin, increased the incidence of gastric ulcers in hyperprolactinaemic rats subjected to cold -plus-restraint stress. These data suggest that the cytoprotective effect of PRL on development of gastric ulcers in stressed animals may involve both central (i.e. dopamine transmission) and peripheral (i.e. prostaglandin synthesis) mechanisms.
