Search

Among numerous regulatory peptide (RP) it is possible to presumably indicate the relict, evolutionary ancient RP. They combine three features: formation from non-specialized proteins-precursors, a comparatively high resistance to action of proteases in the organism media, and maximal simplicity of their structure. The examples of them are glyprolines--a recently identified RP family, as well as tuftsin. Several other praline-containing RP in terminal sites also seem to belong to the evolutionary ancient RP. The proposed approach to studies on the RP evolution is additional to those used traditionally in this problem.

The data and hypotheses on the mechanisms of action of ultrasmall doses (USD) and ultralow concentrations (ULC) of endogenous bioregulators and immunoactive compounds (regulatory peptides, cytokines, etc.) are presented. The reliability of the published data on the effectiveness of USD and ULC within the concentration limits 10(-13) - 10(-24) M and lower is considered.

We propose new approach to classification of regulatory peptides and proteins. It is based on the complex of their properties: stability, affinity to receptors, existence of specialized percursors, protein-transporters etc. In particular we describe very stable factors such as new peptide family named glyprolines.

Our own data and data from the literature on the regulatory role of the simplest proline-containing peptides GP, PG, PGP, GPGG, and cyclic-PG are summarized. These peptides are involved in homeostasis of gastric mucosa and the anticoagulant and fibrinolytic potential of blood plasma. They also potentiate memory consolidation processes in the central nervous system. The most probable sources of these peptides are polypeptide precursors of collagen, elastin, and enterostatin.

An intravenous bolus injection of 0.1 ml alpha-endorphin (1 x 10(-8)-1 x 10(-4) g/ml) didn't change the heart rate in frogs. The parasympathetic bradycardia induced by the peripheral vagus stimulation was decreased by alpha-endorphin. This vago-inhibitory action was dose-dependent (1 x 10(-5)-1 x 10(-4) g/ml). The maximal inhibitory action was watched in 4-8 and 9-15 minutes after bolus injection of alpha-endorphin in concentration of 1 x 10(-5) and 1 x 10(-4) g/ml accordingly.

The interrelationship of the indices of the systolic and diastolic myocardial activity with reference to the cardiac contractions rate was studied in acute experiments in isolated feline hearts. The study had demonstrated that moderate tachycardia (a 30% increase of the cardiac contractions rate) produced a beneficial inotropic effect, and increased the diastolic compliance of the myocardium. Severe tachycardia (a 80--100% increase of the contractions rate) produced a negative inotropic effect decreasing the myocardial compliance. Proceeding from the obtained results a conclusion is drawn that the cardiac contractions rate is an important factor in the regulation of not only the systolic, but also the diastolic myocardial activity.

The cholinolytic effect of sydnophen discovered in earlier anesthetized cats was confirmed on unanesthetized fish and frogs: the vagal bradycardia induced by electric stimulation of peripheral vagal end was decreased or even abolished by intravenous injection of sydnophen (0.2-20 mg/kg). The amphetamine (0.2-30 mg/kg) also blocked the vagal bradycardia in anesthetized cats and unanesthetized frogs. The maximum vagolytic action of amphetamine appeared later (in 4-8 min after injection) in compared with sydnophen (1-3 min). The small dose of amphetamine (0.2-0.3 mg/kg) in contrast to sydnophen didn't decrease the vagal bradycardia but even increased it. It was suggested that the cholinolytic effect of sydnophen and amphetamine is due to different mechanisms.

The influence of the hypertonic (3%) solution of mannitol on the process of the excitability recovery (in the near necrotic zone) appeared as a result of the necroses tissue effect on the ventricle has been investigated in the experiments on the isolated frog's heart. The analogous perfusion was conducted by Ringer solution in the control experiments. The process of isopotential phase S-T recovery was practically the same at heart perfusion with Ringer solution or with mannitol. Simultaneous registration of ventricular mechanogram showed the pronounced negative inotropic effect of mannitol. It is suggested that the positive effect of mannitol which has been noted under clinic conditions during the treatment of ischemic disease, doesn't connect with the effect of hypertonic solution on the cells excitability of periinfarcted (near necrotic) zone.