G. N. Kopylova

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 Amylin on the Tone of Rat Aorta Ring Preparation

Amylin (10-10M) 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.

Effects of glyprolines on stress-induced behavioral disorders in rats.

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 μM/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.

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.

The role of protective effects of proline-containing peptides (PGP, PG, and GP) in contractile dysfunction of mesenteric lymphatic vessels in rats with experimental acute peritonitis.

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.

Glyprolines and Semax Prevent Stress-Induced Microcirculatory Disturbances in the Mesentery

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.

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.

Peptide correction of disorders in rat mesenteric microcirculatory system during inflammation.

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.

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.

Effect of amylin on mast cell secretion as a possible mechanism increasing gastric mucosa resistance.

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 μg/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.