I. P. Ashmarin

Glyprolines in regulatory tripeptides

Glyprolines widely occur in structures of regulatory oligopeptides with a wide spectrum of bioactivities. The role of glyprolines is most significant in regulatory tripeptides. They participate in the stabilization of regulatory oligopeptides in organisms and in the generation of a complex new spectra of bioactivities. Gly-Pro-Glu, Gly-Pro-Leu, Leu-Gly-Pro, Gly-Pro-Arg, Ac-Pro-Gly-Pro, and Gly-Pro-Gly-NH2 serve as examples. The glyprolines deserve further systematic comparative studies. The data in this review can be used to guide elaboration of new peptide medicinal drugs, including hybrid peptides.

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.

[The behavioral effects of beta-casomorphin-7 and its des-Tyr analogs]

The effects of intraperitoneal administration of the heptapeptide beta-casomorphin-7 (beta-K-7) and its des-Tyr analogues (beta-K-6 and beta-K-4) on spontaneous locomotor activity were investigated in rats using Opto-Varimax, RODEO-2 and open field tests. At 20 mg/kg 5 minutes prior to the beginning of measurements beta-K-7 produced a significant decrease in linear locomotion and rearing. As for beta-K-6 and beta-K-4, their influence on locomotion of the experimental animals was less evident. In contrast to beta-K-7, its des-Tyr analogues (20 mg/kg) produced a marked decrease in nose-poking behavior. Beta-K-7 in doses that had no effect on spontaneous behaviour (1 and 5 mg/kg) attenuated extreme behavioural displays under stress conditions. The experimental results suggest the advisability of further investigations of neurotropic properties of beta-K-7 and related peptides.

The Effects of Ante- and Postnatal Hypoxia on the Central Nervous System and Their Correction with Peptide Hormones

Ante- and postnatal hypoxia significantly worsened the postnatal development of animals. The posthypoxic behavioral model included hyperactivity and decreased learning ability, these being typical manifestations of attention deficit disorder. A peptide constellation prevented and significantly improved posthypoxic postnatal development and eliminated the majority of negative behavioral changes.

Improvements in the selective perception and training of rats using an original analog of the C-terminal fragment of vasopressin.

This report presents studies on the effects of intranasal administration of five doses (0.001, 0.01, 0.1, 1, and 10 μg/kg) of a new analog of arginine-vasopressin fragment AVP(6–9), i.e., D-MPRG, on the learning ability of rats with positive and negative reinforcement. All doses of the peptide improved learning. The most effective dose was 0.01 μg/kg, at which the peptide accelerated the acquisition of a conditioned active avoidance reflex both when given 1 h before and when given immediately after training sessions. The peptide had greater effects when animals were trained with negative reinforcement. Analysis of the results suggests that the action of D-MPRG is mainly on perception processes, i.e., extraction of the conditioned stimulus from the environmental surroundings and evaluation and enhancement of its biological significance. In addition, this peptide prevented extinction of the acquired habit and improved the processes of consolidation, though this effect was weaker than its effect on perception.

Hidden Properties of Neuropeptides: Hypnogenic Activity of the Tripeptide Complex DSIP + NPY + ANP

To test the hypothesis that certain peptide complexes can cause effects that cannot be exerted by the same peptides when used separately, the effect of a tripeptide combination of delta sleep-inducing peptide (DSIP), neuropeptide tyrosine (NPY), and atrial natriuretic peptide/factor (ANP/ANF) was studied. In accordance with theoretical vector analysis, such a combination should exert a pronounced anxiolytic effect. Conventional polygraph electrodes and a cannula were preliminarily implanted in the lateral ventricles of rabbits. Peptides (individually or in combination) or a saline solution (control), were administered into the lateral brain ventricle (at a volume of 60–80 µl) at the beginning of the 12-h dark period in experimental chambers. Paperless polygraph recording was continued for 24 h. It was discovered that the tripeptide combination drastically increased hypnogenic activity within the first hours of recording, whereas each peptide alone was either ineffective (DSIP and ANP) or less effective (NPY). We suggest that some neuropeptides may possess a “hidden” physiological activity which becomes evident only after their combined administration or endogenous release.

Structure-function classification of regulatory peptides: What should be included for minimum understanding by a wide variety of neurochemists, neurophysiologists, and senior and post-graduate students

This paper includes proposals for the so-called minimum structure-function classifications of regulatory peptides (RPs) for neurophysiologists and neurochemists and for senior and post-graduate students specializing in the area of neurochemistry and neurophysiology. It is suggested that such classifications should be updated every year on the basis of modern data on RPs and the comments of scientists and high school teachers.

The effects of analogs of the C-terminal fragment of arginine-vasopressin on the dynamics of development of a conditioned active avoidance response in rats

This paper reports studies of the effects of original analogs of the C-terminal fragment AVP (6–9), D-MPR and D-MPRG, on the development of a conditioned active avoidance response in rats; agents were given intranasally over a wide range of doses. The most effective dose of D-MPR was 0.1 μg/kg, and the most effective dose of D-MPRG was 0.01 μg/kg. The tri- and tetrapeptide doses were 10 and 100 times smaller than the dose of arginine-vasopressin used in analogous experimental conditions. The tri- and tetrapeptide accelerated development of the active avoidance conditioned response, affecting both formation of the habit and consolidation of the memory trace. The actions of these peptides were mainly on perception processes, i.e., isolation of the concrete stimulus from the environment, and assessment and remembering of its biological significance.

The effects of a novel analog of the C-terminal fragment of vasopressin on the behavior of white rats

The effects of an arginine-vasopressin fragment, Ac-D-MPRG, on the movement activity and orientational-investigative activity of white rats were studied. Peptide was given intranasally at doses of 0.001, 0.01, 0.1, 1, and 10 μg/kg 1 h before testing. All peptide doses increased vertical movement activity in an open field test and hole board test and decreased grooming levels in both tests. The peptide had no effect on horizontal movement activity. Analysis of these results led to the conclusion that Ac-D-MPRG increases orientational-investigative activity, but, unlike arginine-vasopressin, does not affect non-motivated movement activity.

Nonopioid nature of the pressor effect of FMRF-amide

The effect of the peptide FMRFa on arterial pressure, heart rate, and respiratory rate is examined in anesthetized rats. It is demonstrated that the effect of FMRFa is similar to that of epinephrine and is characterized by transient hypertension against the background of bradycardia and decreased respiratory rate followed by hypotensive phase. Opiate antagonists and agonists do not modify the effect of FMRFa. Pressor effect of FMRFa is inhibited by Aminazine and is abolished by dihydroergotamine, while clopheline, reserpine, propranolol, Dimedrol, and adrenalectomy have no appreciable effect on it. It is suggested that the effects of FMRFa are realized via vascular adrenoreceptors.