A. A. Guseva

Therapeutic effects of glyprolines (PGP, GP, and PG) in rats with stress-induced behavioral disorders

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 µmol/kg prevented stress-induced behavioral disorders. This effect persisted for 3 h.

Effect of peptide Pro-Gly-Pro on stress-induced behavioral changes in rats.

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 organisms response to stress factors.

Secretory Activity of Mast Cell during Stress: Effect of Prolyl-Glycyl-Proline and Semax

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.

Selank and its metabolites maintain homeostasis in the gastric mucosa.

Antiulcer properties of a synthetic anxiolytic Selank and in vivo formed metabolites of this compound were studied on 3 experimental models of ulceration. The test peptides decreased the area of experimental gastric ulcers.

Change in cytokine profile of rats in protective antiulcer effects of glyprolines. Effects of glyprolines (PGP and N-acetyl-PGP) on expression of cytokine genes in ethanol ulcer formation

The effects of glyprolines (PGP and N-acetyl-PGP) on the expression of cytokine genes in the ethanol ulcer formation model have been investigated. Determination of the activity of mRNA in peripheral blood mononuclear cells has been performed using methods of reverse transcription and polymerase chain reaction. It has been shown that, in control animals, the formation of ethanol damages of gastric mucosa in some cases is accompanied by inhibition of transcription of IFN-α, IL-6, IL-12, and TNF-α and increased transcription of IFN-Γ, IL-8, IL-10. PGP reduces the injury area by 38%, which is accompanied by significantly increased gene expression of IL-1β. The peptide Ac-PGP does not change the area of ethanol ulcers but inhibits the transcription of IFN-α, TNF-α (p < 0.05), and IFN-Γ. Thus, the gastroprotective effect of PGP is probably mediated through IL-1β.

Protective and therapeutic effects of glyprolines in psychoemotional stress induced by cholecystokinin-4 injection

Experiments on outbred albino male rats showed that psychoemotional stress induced by intraperitoneal injection of cholecystokinin-4 (100 µg/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 µmol/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.

The protective effect of prolil-glycil-proline peptide (PGP) under compound 48/80-induced anaphylactoid reaction in mice

The influence of PGP on compound 48/80-induced anaphylactoid reaction development in mice and on histamine secretion from rat peritoneal mast cells (RPMS) under their activation by compound 48/80 were investigated. Anaphylactoid reaction was caused by intraperitoneal injection of compound 48/80 into mice. The number of animals with manifestations of anaphylactoid reaction symptoms, the severity of these symptoms, the amount of died animals and the time of death were registering during an hour. Mast cells for in vitro investigations were obtained from rats’ peritoneal cavity. Secreted histamine was evaluated from formation of fluorescent product of it’s condensation with ortho-phthalaldehyde. The preventive injection of PGP in mice (15 min before compound 48/80) decreased the mortality rate of animals and intensity of anaphylactoid reaction symptoms. But PGP had no effect on histamine secretion from mast cells under their activation by compound 48/80 in vitro. Results show that there is a component in the mechanism of PGP protective effect under anaphylactoid reaction which is not connected with mast cells stabilization.

Histomorphological characteristics of accelerated healing of acetate ulcers under the effect of glyprolines.

Glyprolines (PGP, GPG, GPGP, PGPGP, and GPGPGP) modulated histomorphological characteristics of acetate ulcers. They accelerated healing of acetate ulcers, promote complete differentiation of the surface epithelium and glands in the gastric mucosa, contributed to the appearance of a considerable number of fibroblasts at the site of the regenerating mucosa, and significantly decreased the count of macrophages.

Effects of dose and administration mode of endothelin 1 on the mean arterial pressure and heart rate in awake rats

The effects of bolus administration and short-term infusion of endothelin 1 in four doses (2×10−16, 2×10−14, 2×10−12, and 2×10−10 mol/kg) on arterial pressure and heart rate were compared in awake rats. Infusion and bolus administration of the two highest doses increased arterial pressure and provoked bradycardia. Infusion of the two lowest doses increased heart rate without concomitant changes in arterial pressure, while bolus injection of endothelin 1 in the same doses decreased both arterial pressure and the heart rate.

Potentiating effect of thyrotropin-releasing hormone and of its synthetic analog digipramine on morphine-induced analgesia

Thyrotropin-releasing hormone (TRH) and its synthetic analog digipramine (DP) shortened the latency of the tail-flick response in mice when injected intraperitoneally in a dose of 5 mg/kg and to potentiate significantly the analgesic action of morphine. Possible mechanisms of these two effects and prospects for their medical use are discussed.