RESUMEN
Experiments on male outbred albino rats showed that stress (10-min swimming) increased anxiety and inhibited orientation and exploratory activities. Poststress (15 min after the end of swimming) intranasal administration of peptides Pro-Gly-Pro and Gly-Pro in a dose of 3.7 micromol/kg prevented stress-induced behavioral disorders. This effect persisted for 3 h.
Asunto(s)
Dipéptidos/uso terapéutico , Oligopéptidos/uso terapéutico , Trastornos de Estrés Traumático/tratamiento farmacológico , Estrés Psicológico/complicaciones , Animales , Animales no Consanguíneos , Conducta Animal/efectos de los fármacos , Dipéptidos/administración & dosificación , Conducta Exploratoria/efectos de los fármacos , Inyecciones Intraperitoneales , Masculino , Fármacos Neuroprotectores/administración & dosificación , Fármacos Neuroprotectores/uso terapéutico , Oligopéptidos/administración & dosificación , Ratas , Reflejo de Sobresalto/efectos de los fármacos , Trastornos de Estrés Traumático/etiología , Trastornos de Estrés Traumático/fisiopatología , NataciónRESUMEN
We report here studies on the antistress protective actions of three peptides of the glyproline family: Pro-Gly-Pro, Pro-Gly, and Gly-Pro. Stress (10 min forced swimming) evoked typical changes in the behavioral activity of rats in the elevated cross maze and hole board tests, providing evidence of a significant increase in anxiety and a decrease in the level of orientational-investigative activity. Prior (15 min before stress) i.p. administration of Pro-Gly-Pro and Gly-Pro at a dose of 3.7 microM/kg significantly decreased the stress-induced behavioral abnormalities. This demonstrates the possibility that peptides Pro-Gly-Pro and Gly-Pro may affect CNS structures involved in forming the body's responses to stress-inducing factors. Peptide Pro-Gly, at an equimolar dose, had no marked protective effect and only slightly decreased the stress-induced abnormalities in the behavior of rats.
Asunto(s)
Conducta Animal/efectos de los fármacos , Síntomas Conductuales/tratamiento farmacológico , Síntomas Conductuales/etiología , Dipéptidos/uso terapéutico , Fármacos Neuroprotectores/uso terapéutico , Estrés Fisiológico/complicaciones , Animales , Dipéptidos/química , Conducta Exploratoria/efectos de los fármacos , Masculino , Aprendizaje por Laberinto/efectos de los fármacos , RatasRESUMEN
Biologically active peptides evenly labeled with tritium were used for studying the in vitro and in vivo biodegradation of the peptides. Tritium-labeled peptides with a specific radioactivity of 50-150 Ci/mmol were obtained by high temperature solid phase catalytic isotope exchange (HSCIE) with spillover tritium. The distribution of the isotope label among all amino acid residues of these peptides allows the simultaneous determination of practically all possible products of their enzymatic hydrolysis. The developed analytical method includes extraction of tritium-labeled peptides from organism tissues and chromatographic isolation of individual labeled peptides from the mixture of degradation products. The concentrations of a peptide under study and the products of its biodegradation were calculated from the results of liquid scintillation counting. This approach was used for studying the pathways of biodegradation of the heptapeptide TKPRPGP (Selank) and the tripeptide PGP in blood plasma. The pharmacokinetics of Selank, an anxiolytic peptide, was also studied in brain tissues using the intranasal in vivo administration of this peptide. The concentrations of labeled peptides were determined, and the pentapeptide TKPRP, tripeptide TKP, and dipeptides RP and GP were shown to be the major products of Selank biodegradation. The study of the biodegradation of the heptapeptide MEHFPGP (Semax) in the presence of nerve cells showed that the major products of its biodegradation are the pentapeptide HFPGP and tripeptide PGP. The enkephalinase activity of blood plasma was studied with the use of evenly tritium-labeled [Leu]enkephalin. A high inhibitory effect of Semax on blood plasma enkephalinases was shown to arise from its action on aminopeptidases. The method, based on the use of evenly tritium-labeled peptides, allows the determination of peptide concentrations and the activity of enzymes involved in their degradation on a tg scale of biological samples both in vitro and in vivo.
Asunto(s)
Oligopéptidos/farmacocinética , Tritio , Hormona Adrenocorticotrópica/análogos & derivados , Hormona Adrenocorticotrópica/farmacocinética , Aminopeptidasas/sangre , Aminopeptidasas/metabolismo , Animales , Encéfalo/metabolismo , Cromatografía Líquida de Alta Presión , Encefalina Leucina/metabolismo , Encefalinas/sangre , Encefalinas/metabolismo , Hidrólisis , Técnicas In Vitro , Marcaje Isotópico , Neprilisina/antagonistas & inhibidores , Neprilisina/metabolismo , Oligopéptidos/química , Fragmentos de Péptidos/farmacocinética , Ratas , Ratas Sprague-DawleyRESUMEN
Protective and antistress effects of three glyprolines--PGP, PG and GP, were studied. Stress influences produced typical changes of behavioural activity of rats in the elevated pluz-maze and the hole-board tests. These changes suggest a significant enhancement of anxiety and a drop of the level of orientation-investigative activity. A preliminary (15 minutes before stress agent) intraperitoneal administration of PGP or GP in doses of 3.7 microm/kg significantly decreased stress disturbances of behaviour. Analysis of these data shows to the possibility of PGP and GP influences on the CNS structures, which take part in the organism reciprocal reactions to stress factor. The peptide GP at equimolar dose didn't possess pronounced protective properties and just slightly decreased stress disturbance of behavioural activity of rats.
Asunto(s)
Conducta Animal/efectos de los fármacos , Dipéptidos/administración & dosificación , Aprendizaje por Laberinto/efectos de los fármacos , Estrés Fisiológico/fisiopatología , Animales , Inyecciones Intraperitoneales , Masculino , RatasRESUMEN
On the experimental model of denervation-reinnervation syndrome of mouse shank muscles neurotrophic effects of jashaltinsky medicinal mud were studied. In experimental mice therapeutic mud has been applied on the small back, tail and rib areas of the body 10 days after nerve crushing. On day 11 after nerve crushing a stable reproduction of a compound nerve action potential with constant amplitude was revealed in repetitive (50 Hz) nerve stimulation.
Asunto(s)
Peloterapia , Desnervación Muscular , Músculo Esquelético/inervación , Regeneración Nerviosa/efectos de los fármacos , Nervio Peroneo/fisiología , Neuropatías Peroneas/terapia , Animales , Modelos Animales de Enfermedad , Masculino , Ratones , Músculo Esquelético/efectos de los fármacos , Nervio Peroneo/efectos de los fármacos , SíndromeRESUMEN
Tripeptide PGP in a dose of 1 mg/kg had a correcting effect on behavioral disorders in rats induced by stress exposure (forced swimming). PGP prevented the increase in anxiety and decrease in orientation and exploratory activity. Our results suggest that the effect of this peptide is realized via central nervous structures involved in organism's response to stress factors.