A. A. Kamenskii

The neuroprotective effects of Semax in conditions of MPTP-induced lesions of the brain dopaminergic system.

This report describes studies of the effects of the ACTH(4–10) analog Semax (MEHFPGP) on the behavior of white rats with lesions to the brain dopaminergic system induced by the neurotoxin MPTP. Neurotoxin was given as single i.p. doses of 25 mg/kg. Neurotoxin injections were shown to decrease movement activity and increase anxiety in the animals. Daily intranasal administration of Semax at a dose of 0.2 mg/kg decreased the severity of MPTP-induced behavioral disturbances. The protective activity of Semax in MPTP-induced lesions of the brain dopaminergic system may be associated with both its modulating effect on the dopaminergic system and the neurotrophic action of the peptide.

Delayed behavioral effects of β-casomorphin-7 depend on age and gender of albino rat pups

Systemic administration of β-casein heptapeptide β-casomorphin-7 (YPFPGPI, 1 mg/kg daily) to 10–23-day-old albino rat pups produced delayed anxiolytic effects, which were more pronounced in female than in male rats. Experimental findings confirm our assumption on the important role of nutritional opioids in brain development in newborn mammals.Systemic administration of β-casein heptapeptide β-casomorphin-7 (YPFPGPI, 1 mg/kg daily) to 10–23-day-old albino rat pups produced delayed anxiolytic effects, which were more pronounced in female than in male rats. Experimental findings confirm our assumption on the important role of nutritional opioids in brain development in newborn mammals.

Effects of single intranasal administration of obestatin fragments on the body weight and feeding and drinking behaviors.

336 Lately, there has been a growing body of evidence about endogenous peptide regulators of appetite. Par ticular attention among them is paid to obestatin, which is a derivative of preproghrelin and composed of 23 amino acid residues [1]. An anorexigenic effect of obestatin has been shown in a number of studies [1, 2]. However, the study of anorexigenic effects of obestatin fragments are of a special interest. According to some data, fragment 1–13 has the strongest anorexigenic effect [3]; according to others, fragment 11–23 has [4]. There has been almost no analysis of the effects of other fragments. Therefore, we have investigated the effects of different obestatin fragments on body weight changes and the intake of food and water given ad libi tum. For our study, we chose fragments 1–4, 5–10, and 10–15 as less studied ones and fragment 11–23 whose anorexigenic effect had been shown earlier.

Comparative analysis of neurotropic activity of exorphines, derivatives of dietary proteins

The effects of wheat gluten fragments, hemoglobin, and milk β-caseins (exorphine C, hemorphine-6, and β-casomorphine-7) on nociceptive sensitivity and behavior were studied in albino rats. Hemorphine-6 and exorphine C induced hyperalgesia and increased anxiety; β-casomorphine-7 decreased anxiety and nociceptive sensitivity. All peptides partially decreased motor activity and the orientative-exploring reaction. In contrast to β-casomorphine-7, exorphine C and hemorphine-6 did not exhibit neurotropic activity intrinsic to opioids and can be characterized as functional antagonists of endogenous opioid peptides.

Effect of tuftsin on the functional activity and intracellular pH of murine peritoneal macrophages

The effect of tuftsin and its tripeptide analog in various concentrations (from 0.001 to 10.0 μg/ml) on phagocytosis and on the intracellular pH is studied in murine peritoneal macrophages. Tuftsin causes a uniform dose-dependent increase of these two parameters in the cells. This effect is maximally pronounced at concentrations of the peptide close to its physiological level (about 0.3 μg/ml) and gradually decreases as its content in the incubation medium is lowered or raised. On the other hand, the tripeptide analog of tuftsin does not exhibit such an effect on the cells and under the same conditions suppresses phagocytosis and acidifies their intracellular medium.

The antithrombotic and thrombolytic activity of tuftsin

It has been established that one of the immune regulatory peptides, tuftsin, with the amino acid sequence Thr-Lys-Pro-Arg, has a depolymerizing effect on fibrin [21 and prevents its polymerization [5]. It has also been shown that tuftsin displays anticoagulant properties [4], which are related to the sequence Pro-Arg [10]. Normal blood contains around 300 gg/liter of tuftsin [8]. Such a concentration in in vitro experiments produces a fibrinolytic effect [4]. Tuftsin may interact in vitro with high-molecular heparin, resulting in the formation of a complex [6] possessing anticoagulant and fibrinolytic properties. Interaction with heparin in vivo may result in a rise of the anticoagulant and fibrinolytic potential of the blood [4]. The capacity of tuftsin to produce antithrombotic and thrombolytic activity in the organism was examined in the present study.

Changes in feeding and drinking motivations and glucose content in male rats after single or chronic administration of obestatin or its fragment (1–4)

Obestatin is an endogenous regulator of appetite with anorexigenic action. In this study, we analyzed the effects of single and chronic intranasal administra� tions of obestatin or its fragment (1–4) at a dose of 300 nmol/kg on the glucose content of blood and food and water motivation under the conditions of depriva�

Delayed effect of exorphins on learning of albino rat pups

The delayed effect of food-derived opioid peptides (exorphins) after chronic administration on postnatal days 1–14 on the learning of albino rat pups has been studied. Heptapeptide YPFPGPI (β-casomorphin-7), pentapeptide YPLDL (rubiscolin-5) and pentapeptide YPISL (exorphin C) improved the development of the conditioned foraging reflex in a complex maze. Hexapeptide PFPGPI lacking the N-terminal tyrosine proved inefficient. Only β-casomorphin-7 had an effect (negative) on passive avoidance conditioning. The obtained data confirm that exorphins (particularly, milk-derived β-casomorphins) can have significant and long-term effects on the environmental adaptation of young mammals.

Comparative study of analgesic potency of ACTH4–10 fragment and its analog semax

The effects of ACTH4–10 fragment and its analog semax on nociception were examined on various animal models. ACTH4–10 in a dose of 0.5 mg/kg decreased nociception in rats during hindpaw compression test and in mice subjected to acetic acid writhing test. Lower doses of ACTH4–10 produced no analgesic effect. Semax (0.015–0.500 mg/kg) decreased pain sensitivity in all experimental models. Hence, the substitution of three C-terminal amino acid residues in ACTH4–10 for Pro-Gly-Pro sequence augmented the analgesic potency of the peptide after its peripheral injection.

Activation of maternal behavior of albino rats after combined treatment with dopamine and opioid receptor antagonists in low doses

We studied the effect of D1/D2 antagonist haloperidol on maternal motivation in nursing albino rats. Haloperidol in a dose of 0.2 mg/kg significantly attenuated parental reactions and motor and exploratory activities. In a lower dose (0.1 mg/kg) the drug produced the same effect on maternal behavior (number of approaches to newborns) without reducing motor activity. The effect of low-dose haloperidol was different after naloxone treatment (0.2 mg/kg intranasally): the number of pup transfers increased significantly. The detected phenomenon indicates good prospects of combined treatment with agents modifying the cerebral dopaminergic and opioid systems as the method for correction of disorders in maternal behavior.