Falalyeyeva T. The role of glutamate and proline comprising di- and tripeptides in the regulation of morpho-functional state of the stomach

Українська версія

Thesis for the degree of Doctor of Science (DSc)

State registration number

0511U000758

Applicant for

Specialization

  • 03.00.13 - Фізіологія людини і тварин

19-10-2011

Specialized Academic Board

Д 26.001.38

Taras Shevchenko National University of Kyiv

Essay

The study is dedicated to the investigation of the role of glutamate and proline comprising di- and tripeptides in the regulation of morpho-functional state of the stomach. With pharmacological analysis and surgical denervation of the stomach it was determined multidirectional role of central and peripheral ionotropic glutamate receptors: stimulation of central glutamate receptors (NMDA and kainate subtypes) causes increased gastric acid secretion (GAS), in contrary stimulation of peripheral glutamate kainate subtype receptors causes inhibition of hydrochloric acid secretion. Glutamate AMPA subtype receptors aren't involved in regulation of GAS. For the first time it was shown that prolonged administration of monosodium glutamate resulted in a disturbance of morpho-functional state of the stomach: hypersecretion of hydrochloric acid, the development of erosive and ulcerative lesions of the gastric mucosa (GM), morphological changes of the mucosa, as well as the development of obesity. These pathological changes didn't develop under conditions of simultaneous application of glutamate and proline comprising di- and tripeptides (glyprolines). It was established that glyprolines (Pro-Gly-Pro and Gly-Pro) inhibited basal GAS and GAS stimulated with carbacholine, histamine and pentagastrin in rats. Vagotomy completely eliminated inhibitory effect of Pro-Gly-Pro and Gly-Pro on GAS, stimulated with carbacholine and diminished basal and stimulated with histamine and pentagastrin secretion, which is the evidence that these effects depend on the tonic influence of central nervous system transmitted by the vagus nerve. Pro-Gly didn't affect GAS stimulated with carbachol, histamine and pentagastrin in rats. It was found that the mechanism of preventive action of glyprolines on the development of lesions of various origins in GM is not only the stimulation of nitric oxide release and improving in blood supply of GM, but also the normalization of pro- and antioxidant balance of the total fraction of mucosal cells and the stabilization of glycoproteid composition in the tissues of GM. Field of the use: physiology, gastroenterology, biochemistry, pharmacology.

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