RESUMEN
The development of inflammation (experimental model of peritonitis induced by administration of sodium thioglycolate) was accompanied by a decrease in osmotic resistance of erythrocytes. Changes in osmotic resistance of erythrocytes associated with preliminary (15 min before induction of inflammation) administration of peptide Pro-Gly-Pro were significantly weaker, and the percentage of hemolyzed cells was reduced. The peptide injected against the background of developed inflammation (1 h 45 min after induction) had no corrective effect on osmotic resistance. During in vitro experiments, Pro-Gly-Pro did not affect hemolysis of intact erythrocytes. These results support the assumption that prophylactic administration of the peptide protects erythrocyte membranes and increases their osmotic resistance.
Asunto(s)
Eritrocitos/efectos de los fármacos , Inflamación/tratamiento farmacológico , Oligopéptidos/farmacología , Presión Osmótica/efectos de los fármacos , Prolina/análogos & derivados , Animales , Células Cultivadas , Oligopéptidos/uso terapéutico , Prolina/farmacología , Prolina/uso terapéutico , RatasRESUMEN
Injection of substance 48/80 to rats led to dysfunction of mesenteric lymphatic microvessels, in particular inhibition of their contractility and modification of their reaction to norepinephrine. Injection of PGP peptide before and after substance 48/80 alleviated these disorders. The results indicated the possibility of peptide correction of lymphatic vessel dysfunction.
Asunto(s)
Vasos Linfáticos/efectos de los fármacos , Norepinefrina/administración & dosificación , Oligopéptidos/uso terapéutico , Prolina/análogos & derivados , p-Metoxi-N-metilfenetilamina/análogos & derivados , p-Metoxi-N-metilfenetilamina/administración & dosificación , Animales , Inyecciones Intramusculares , Vasos Linfáticos/fisiopatología , Masculino , Mesenterio/efectos de los fármacos , Prolina/uso terapéutico , RatasRESUMEN
We studied the effect of acute (single immobilization for 1 h) and repeated (daily immobilization for 1 min, 5 days) moderate stress on disturbances in contractility of mesenteric lymphatic vessels in rats with experimental peritonitis. Acute stress was shown to potentiate, while moderate repeated stress attenuate the effect of inflammatory stimulus. It can be hypothesized that moderate repeated stress improves adaptive capacities of the organism, which manifests in reduction or prevention of dysfunction in contractile activity of lymphatic vessels.
Asunto(s)
Inflamación/fisiopatología , Vasos Linfáticos/fisiología , Mesenterio/irrigación sanguínea , Restricción Física/fisiología , Estrés Fisiológico/fisiología , Animales , Inflamación/inducido químicamente , Masculino , Ratas , Tioglicolatos/toxicidadRESUMEN
Experiments on outbred albino male rats showed that psychoemotional stress induced by intraperitoneal injection of cholecystokinin-4 (100 microg/kg) increased anxiety, impaired orientation and exploration activities in the elevated plus-maze and hole-board tests, and increased the level of depression of Porsolt test. Preliminary intranasal administration of glyprolines (15 min before cholecystokinin) in a dose of 3.7 micromol/kg prevented the development of stress-induced behavioral disturbances. Administration of peptides 30 min after cholecystokinin-4, i.e., to rats with developed behavioral disturbances, almost completely abolished these disturbances.
Asunto(s)
Dipéptidos/uso terapéutico , Oligopéptidos/uso terapéutico , Prolina/análogos & derivados , Estrés Psicológico/tratamiento farmacológico , Animales , Ansiedad/inducido químicamente , Ansiedad/tratamiento farmacológico , Conducta Animal/efectos de los fármacos , Depresión/inducido químicamente , Conducta Exploratoria/efectos de los fármacos , Masculino , Aprendizaje por Laberinto/efectos de los fármacos , Prolina/uso terapéutico , Ratas , Estrés Psicológico/inducido químicamente , TetragastrinaRESUMEN
The distribution of the glyprolines Pro-Gly-Pro and Thr-Lys-Pro-Arg-Pro-Gly-Pro (Selanc) was analyzed and compared in tissues of rat organs after different ways of their administration using the peptides uniformly labeled with tritium. Comparative data on changes in concentrations of the peptides in the rat organs after their intraperitoneal, intranasal, intragastric, and intravenous administration are given. The intranasal administration of both peptides was shown to be optimal for the delivery of glyproline molecules in the CNS. A high affinity of the studied glyprolines for gastric tissues was found for all the ways of their administration. We suggest that a high efficiency of action of glyprolines on homeostasis of the gastric mucous tunic was partially provided by accumulation of these peptides (to high concentrations) in gastric tissues.
Asunto(s)
Oligopéptidos/farmacocinética , Prolina/análogos & derivados , Animales , Vías de Administración de Medicamentos , Mucosa Gástrica/metabolismo , Oligopéptidos/administración & dosificación , Prolina/administración & dosificación , Prolina/farmacocinética , Ratas , Distribución TisularRESUMEN
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
PGP peptide had a protective effect in contractile dysfunction of the rat mesenteric lymph vessels under conditions of inflammation, irrespective of the time of its injection (before or after inflammatory agent). The preventive effect of this peptide is largely determined by its capacity to prevent mast cells activation. PGP injected 2 h after induction of inflammation did not inhibit secretory activity of mast cells, which suggests other mechanisms of its therapeutic action.
Asunto(s)
Mesenterio/irrigación sanguínea , Oligopéptidos/farmacología , Peritonitis/fisiopatología , Prolina/análogos & derivados , Animales , Vasos Linfáticos/efectos de los fármacos , Vasos Linfáticos/fisiología , Masculino , Mastocitos/efectos de los fármacos , Mastocitos/fisiología , Microcirculación/efectos de los fármacos , Norepinefrina/farmacología , Peritonitis/inducido químicamente , Prolina/farmacología , Ratas , TioglicolatosRESUMEN
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
A peptide acidic hydrolysate of collagen (PHC) was obtained under conditions (4 N HCl) ensuring the predominant formation of short peptides, glyprolines. They were separated and their antiulcer activity was studied. Thirty individual peptides with molecular masses of 174-420 amu were isolated from the PHC by HPLC. The PHC was shown to predominantly contain 2- to 4-aa peptides, including PG, GP, and PGP. Experiments on rats demonstrated that, on intragastric administration at a dose of 1 mg/kg, PHC enhances the stability of the gastric mucosa to the action of ulcerogenic factors, such as ethanol and stress, and exhibits a protecting antiulcer effect. Even a lesser dose (0.1 mg/kg), which reduced ulcer area twofold, was effective in the stress model of ulcer formation. The intraperitoneal and intragastric administration of PHC at a dose of 1 mg/kg was found to exhibit a therapeutic effect in the acetate model of ulcer formation.
Asunto(s)
Antiulcerosos/uso terapéutico , Colágeno/química , Fragmentos de Péptidos/uso terapéutico , Úlcera Gástrica/tratamiento farmacológico , Animales , Antiulcerosos/química , Cromatografía Líquida de Alta Presión , Etanol , Mucosa Gástrica/efectos de los fármacos , Hidrólisis , Masculino , Fragmentos de Péptidos/química , Ratas , Ratas Wistar , Úlcera Gástrica/etiología , Estrés Psicológico/complicacionesRESUMEN
The development of acute peritonitis in rats induced by intraperitoneal injection of thioglycollate was accompanied by a decrease in contractile function of mesenteric lymphatic vessels and impaired response to norepinephrine. Administration of proline-containing peptides after induction of inflammation significantly decreased the severity of these disorders. Our results attest to the possibility of using peptides for the correction of mesenteric microcirculatory disturbances during inflammation.
Asunto(s)
Vasos Linfáticos/fisiopatología , Mesenterio/irrigación sanguínea , Péptidos/uso terapéutico , Peritonitis/tratamiento farmacológico , Prolina/uso terapéutico , Sustancias Protectoras/uso terapéutico , Enfermedad Aguda , Animales , Inyecciones Intraperitoneales , Cinética , Mesenterio/fisiopatología , Péptidos/administración & dosificación , Peritonitis/inducido químicamente , Peritonitis/patología , Prolina/administración & dosificación , Prolina/química , Sustancias Protectoras/administración & dosificación , Ratas , Tioglicolatos/toxicidadRESUMEN
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
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.
Asunto(s)
Conducta Animal/efectos de los fármacos , Oligopéptidos/farmacología , Prolina/análogos & derivados , Prolina/farmacología , Estrés Psicológico , Animales , Animales no Consanguíneos , Ansiedad/prevención & control , Conducta Exploratoria/efectos de los fármacos , Inyecciones Intraperitoneales , Masculino , Orientación/efectos de los fármacos , Ratas , Natación , Factores de TiempoRESUMEN
Amylin belongs to the calcitonin peptide family. Amylin is a peptide synthesized not only in the beta cells of pancreatic islets, but in small quantities also in other organs like in the intestinal and gastric mucosa, lungs and central nervous system. It is located in the same secretory granules as insulin. Amylin participates in the maintenance of glucose and calcium homeostasis. It also inhibits food intake and decreases body weight. Furthermore, amylin inhibits gastric acid secretion. It protects the gastric mucosa in ulcer models like stress, vagal stimulation, ethanol, acetic acid, reserpine and serotonine administration and pylorus ligation. This protective antiulcer is seen not only at pharmacological but also at near-physiological doses-0.5mkg/kg. Moreover amylin also exerts curative properties in the acetic acid and indomethacin ulcer models. Amylin decreases the aggressive factors like acid-pepsin secretion, increases mast cell stability and increases protective mechanisms like bicarbonate gastric secretion, dilates blood vessels, and it increases lymphatic mesenteric activity. Amylin seems to be a powerful protector of gastric mucosa in animals by increasing the stability of gastric mucosa. Further research remains, however, to be done.
RESUMEN
Intraperitoneal injection of cholecystokinin-4 in a dose of 100 mg/kg markedly increased secretory activity of mast cells in the mesentery and subcutaneous fat. These changes developed 5 min after treatment and progressed in time. Over the first 15 min we observed primarily merocrine secretion (granulolysis), while 60 min after cholecystokinin-4 administration apocrine secretion (degranulation) prevailed. In vitro cholecystokinin-4 had no effect on secretory activity of mast cells. Our findings suggest that stimulation of secretory activity of mast cells is determined by psychoemotional stress associated with activation of the sympathoadrenal and hypothalamic-pituitary-adrenal systems.
Asunto(s)
Mastocitos/metabolismo , Estrés Psicológico/fisiopatología , Tetragastrina/farmacología , Animales , Masculino , Ratas , Estrés Psicológico/inducido químicamenteRESUMEN
Stress increased secretory activity of mast cells in the mesentery and subcutaneous fat of rats. Intraperitoneal injection of Semax and prolyl-glycyl-proline in doses of 0.05 and 1 mg/kg, respectively, 1 h before stress abolished this effect. The test preparations did not modulate secretory activity of mast cells in unstressed animals. Semax and prolyl-glycyl-proline in vitro prevented activation of mast cells with synacten and acetylcholine. The stabilizing effect of peptides on mast cells probably determines their antiulcer activity.
Asunto(s)
Hormona Adrenocorticotrópica/análogos & derivados , Hormona Adrenocorticotrópica/farmacología , Mastocitos/metabolismo , Oligopéptidos/farmacología , Fragmentos de Péptidos/farmacología , Prolina/análogos & derivados , Prolina/farmacología , Estrés Psicológico/inducido químicamente , Acetilcolina/metabolismo , Hormona Adrenocorticotrópica/administración & dosificación , Animales , Animales no Consanguíneos , Modelos Animales de Enfermedad , Inyecciones Intraperitoneales , Masculino , Mastocitos/citología , Mastocitos/efectos de los fármacos , Mesenterio/citología , Mesenterio/efectos de los fármacos , Mesenterio/fisiopatología , Oligopéptidos/administración & dosificación , Fragmentos de Péptidos/administración & dosificación , Prolina/administración & dosificación , Ratas , Estrés Psicológico/fisiopatologíaRESUMEN
One-hour immobilization stress considerably disturbed microcirculation in the mesentery: blood flow in small mesenteric vessels decreased or stopped and numerous hemorrhages appeared. Lymphatic vessels lost spontaneous activity and did not respond to norepinephrine. Administration of Semax and glyprolines 1 h before stress decreased the severity of stress-induced microcirculatory disturbances. PGP and GP were most effective in this respect.
Asunto(s)
Hormona Adrenocorticotrópica/análogos & derivados , Hormona Adrenocorticotrópica/farmacología , Mesenterio/irrigación sanguínea , Microcirculación/efectos de los fármacos , Fragmentos de Péptidos/farmacología , Prolina/farmacología , Animales , Hemorragia/tratamiento farmacológico , Hemorragia/fisiopatología , Inmovilización , Masculino , Mesenterio/fisiopatología , Microcirculación/fisiología , Microcirculación/fisiopatología , Norepinefrina/farmacología , Oligopéptidos/química , Oligopéptidos/farmacología , Prolina/análogos & derivados , Ratas , Flujo Sanguíneo Regional/efectos de los fármacos , Flujo Sanguíneo Regional/fisiología , Estrés Fisiológico/tratamiento farmacológico , Estrés Fisiológico/etiología , Estrés Fisiológico/fisiopatologíaRESUMEN
Water-immersion restraint stress increased secretory activity of mast cells and led to the formation of erosive lesions in the gastric mucosa. Intraperitoneal administration of amylin in a dose of 0.5 microg/kg 1 h before stress suppressed degranulation of mast cells and decreased the severity of gastric mucosa damages. In in vitro experiments amylin abolished the activating effects of acetylcholine and bradykinin on mast cell degranulation. Amylin-induced stabilization of activated mast cells probably underlies its protective effects during ulceration.
Asunto(s)
Amiloide/farmacología , Mucosa Gástrica/efectos de los fármacos , Mastocitos/metabolismo , Acetilcolina/metabolismo , Animales , Bradiquinina/metabolismo , Inyecciones Intraperitoneales , Polipéptido Amiloide de los Islotes Pancreáticos , Masculino , Ratas , Ratas Wistar , Úlcera/patología , Agua/metabolismoRESUMEN
Amylin (10(-10)M) induced relaxation of norepinephrine-precontracted rat aortic rings by more than 50%. This effect was preserved after blockade of NO-synthase and even after denudation of the vessel. Thus amylin-induced vasodilation is an endothelium-independent process not mediated by NO.