Biomedical subjects
Publications and source records attributed to A P Smirnova.
A total chemical synthesis of [Ala5, Orn9]somatostatin has been performed. This structural analogue of natural somatostatin inhibits the release of somatotropin, insulin and glucagon, but shows no inhibitory effect on secretion of prolactin.
In chronic experiments on dogs, microapplication of neurotensin into the hypothalamus or amygdala combined with histamin or pentagastrin stimulation of the stomach secretory function significantly reduced the stomach secretion. Microapplication of somatostatin into the hypothalamus or amygdala combined with i.v. administration of pentagastrin increased two-fold the stomach secretion. The same increasing effect occurred after microapplication of methionin or leucin-5-enkephalin retroanalogue into the hypothalamus or amygdala.
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I.v. administration of somatostatin (1.5 micrograms/kg/g) reduced the gastric secretion induced by pentagastrin and histamine. Microapplication of somatostatin to globus pallidus (10 micrograms in 3 ml) increased the acid secretion in the dog stomach. The serum gastrin level was decreased both in the i.v. administration of somatostatin and in its cerebral application.
A comparative study of labelled thyroxine and iodine accumulation was carried out in the thyroid endocrine complex under endoliquor and intraabdominal introduction of thyrotropic hormone (TTH) and thyrotropin-releasing-factor (TRF) in rats with transplantable and induced tumours as well as in intact animals. A sharp decrease of the system response to TRF in tumour-bearing animals was established. The incorporation of labelled thyroxine introduced into the thyroid gland tissue and posterior region of the hypothalamus is found to be lower under the tumour growth. The character of changes causing the disturbances in the activity of the thyroid gland should be taken into account in an attempt to normalize the gland activity. The normalization should be based on the complex influence directed to all the links of the hypothalamus-pituitary thyroid gland system.
TRH and its two analogs with modified hormonal activity were examined for the capacity to antagonize acute and chronic effects of ethanol in mice. It has been demonstrated that L-pyroglutamyl-L-seryl-L-leucinamide, an analog of TRH, that does not affect the secretion of TSH and decreases prolactin production has the same capacity as TRH to reduce the time of ethanol narcosis but produces a lesser effect on the ethanol-induced fall of rectal temperature. Both the drugs did not affect the ethanol-altered ability of mice to hold on the rotating bar. Methyl ether of TRH, a hormonally inactive analog, was ineffective as shown by all the tests. Neither TRH nor its analogs changed the development of tolerance to chronic administration of ethanol, recorded by the rotating bar test and rectal temperature drop.
Alteration of the enkephalin molecule by means of synthesis of peptide with opposite direction of peptide connections between residues of aminoacids (retro--methionin--5--enkephalin) entailed some changes of its action in respect to activity of the stomach secretory cells in dogs. Thus, for instance, the retroanalogue methionin--5--enkephalin proved to be a more efficient activator of gastric secretion induced with pentagastrin.
The synthesis of retro-analog of methionine-5-enkephalin was performed. This peptide is an isomer of the natural methionine-5-enkephalin, but differs from it by opposite direction of peptide linkages between the amino acid residues. The influence of retro-analog on prolactin secretion was studied both in vivo and in vitro. The retro-analog was found to stimulate the prolactin secretion more effectively than methionine-5-enkephalin.
A study was made of susceptibility of hypothalamic neurons to beta-endorphine, thyroliberin and met-enkephalin applied microiontophoretically. The opioids were shown to exert a primarily unidirectional effect on the same neurons irrespective of the fact that the inhibitory action of beta-endorphine was more pronounced. The nalorphine-competitive antagonist of the opiates removed the met-enkephalin-induced inhibition. Unlike opioids, thyroliberin largely activated the test neurons. The possibility of neuropeptide participation in the control of gonadotropic function of the pituitary is discussed.
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A study was made of the effect of replacement of the second and third amino acid residues of the thyrotropin-releasing hormone on the manifestation of the specific biological activity assessed by the radioimmune method of determination of the thyrotropic hormone in rats. Replacement of histidine by alanine caused a 100-fold and by phenylalanine - a 10-fold reduction of the activity. Glycine analogue proved to be inactive. The biological activity of TRH analogue (Glu-Phe-Pro CH3) was only 10 times less in comparison with the activity of the standard. The second double modified analogue of this hormone (Glu-Gly-Ser NH2) was incapable of influencing the release of the thyrotropic hormone by the hypophysis.
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The effect of synthetic somatostatin on the basal and stimulated secretion of growth hormone and prolactin under conditions of incubation of the adenohypophysis (ADH) tissue in vitro was studied. The labeled growth hormones (GH) and prolactin (Pl) secreted was assayed by the method of electrophoresis in polyacrylamide gel as modified by the authors. Synthetic somatostatin (10 and 100 nM) suppressed the basal and stimulated by 2--0-dibutyril AMP, theophylline, and prostaglandins of E series GH labeled secretion. In doses of 100 nM the inhibitor also suppressed the basal and the stimulated by 2--0-dibutyril AMP and theophylline release of labeled Pl. Apparently, the inhibitory action of somatostatin involves the reduction of the ADH activity of adenylatecyclase.
Ability of Ala5, Orn9-somatostatin to inhibit the secretion of insulin, glucagon, somatotropic hormone (STH) and prolactin was tested on the model of primary monolayer culture of isolated insular pancreatic and adenohypophyseal cells. Chemical substitution performed between positions 5 and 9 in somatostatin molecule failed to change essentially hormone's biologic activity in suppression of insulin and glucagon in the culture of pancreatic insular cells isolated from newborn rats. Somatostatin analog revealed its natural hormonal ability to inhibit STH secretion but failed to affect that of prolactin. The results are suggestive of the principal possibility to produce somatostatin biologically active analog through lyzine residue substitution in position 9 with obligatory simultaneous substitution amino acid residue in position 5.