The role of mu- and delta-opiate receptors in resistance of the myocardium to free radical damage]

I.v. administration of the delta-opioid (OR) receptors' agonists DSLET or DTLET prevented creatine kinase leakage from the rat isolated heart in oxidative stress damage and abolished an increase in myocardial levels of conjugated diens and malondialdehyde. The agonists also prevented a stress-induced augmentation of the superoxide dismutase (SOD) activity. All protective effects of delta-receptor stimulation was completely abolished by the delta OR antagonist ICI 174,864. The data obtained suggest that the cardioprotective effect of the delta OR stimulation in vivo is not mediated via direct cardiac delta OR activation but, probably, rather via some unknown indirect circulating humoral factor(s).     

The role of mu- and delta-opiate receptors in the realization of the autonomic effects of opioid peptides

In the first series of experiments on the isolated mouse vas deferens and guinea-pig ileum the capacity of 10 opioid peptides to activate mu- and delta-receptors was evaluated. [DAla2, DLeu5]-enkephalin (DADLE) and [DAla2, MePhe4, Gly5-ol]-enkephalin (DAMPGE) were the most selective agonists of delta- and mu-opiate receptors, respectively. In the second series of experiments on urethan-anesthetized rats it was shown, that intravenous administration of DADLE or DAMPGE (10(-7) M/kg each) elicited hypotension, bradycardia and expiratory apnoe. These effects disappeared both after naloxone injection and bilateral cervical vagotomy. A reflex nature of the vegetative effects of opioid peptides and the role of both mu- and delta-receptors in their realization are suggested.     

Influence of hydrocortisone and adrenaline against the background of mu- and delta-opiate receptors blockade on local immune response in mice

In the induced phase of the immune response, the immunosuppressive effects of hydrocortisone and adrenaline were enhanced under mu- and delta-opiate receptor blockade. No changes were observed in the effects of hydrocortisone and adrenaline under mu- and delta-opiate receptor blockade in effector phase. In the induced phase of the immune response, selective agonists of mu- and delta-opiate receptors DAGO and DADLE enhanced antibody response, delayed-type hypersensitivity, and reduced the number of cells in the regional lymph node. Thus, our data suggest an equal role of mu- and delta-opiate receptors in regulation of expressiveness of local immune response.     

The immunomodulating action of myelopeptides in hypoxic hypoxia in animals

It was observed that in animals which underwent a hypoxic stress by way of a 3-day exposition in the pressure chamber at an altitude of 7,000 m the immune response to sheep erythrocytes was decreased by 47 per cent. A two-three-fold decrease in the production of myelopeptides was noted in 24h after the exposition in the pressure chamber.     

Participation of central and peripheral mu- and delta opiate receptors in anti-arrhythmia action of enkephalins]

It was found, that injection of delta-receptors agonist dalargin before the occlusion of left anterior coronary artery in rats prevented the decrease of ventricular fibrillation threshold (VFT). An injection of naloxone in dose 0.5 mg/kg (for the blockade of mu-receptors only) had no influence on the VFT. Naloxone in dose 1 mg/kg (for the blockade peripheric mu- and delta-receptors) decreased VFT. An intraventricular infusion of dalargin (10 mkg) induced bradycardia and an increase of VFT. It was assumed that anti-arrhythmic effects of enkephalins in acute myocardial ischemia could be realized by an activation of peripheric delta-receptors and central mu-receptors.     

Affinity labeling of delta-opiate receptors using [D-Ala2,Leu5,Cys6]enkephalin. Covalent attachment via thiol-disulfide exchange

[D-Ala2,Leu5,Cys6]Enkephalin (DALCE) is a synthetic enkephalin analog which contains a sulfhydryl group. DALCE binds with high affinity to delta-receptors, with moderate affinity to mu-receptors, and with negligible affinity to kappa-receptors. Pretreatment of rat brain membranes with DALCE resulted in concentration-dependent loss of delta-binding sites. Using 2 nM [3H][D-Pen2,D-Pen5]enkephalin (where Pen represents penicillamine) to label delta-sites, 50% loss of sites occurred at about 3 microM DALCE. Loss of sites was not reversed by subsequent incubation in buffer containing 250 mM NaCl and 100 microM guanyl-5'-yl imidodiphosphate (Gpp(NH)p), conditions which cause dissociation of opiate agonists. By contrast, the enkephalin analogs [D-Ala2,D-Leu5]enkephalin, [D-Ser2,Leu5,Thr6]enkephalin, [D-Pen2,D-Pen5]enkephalin, and [D-Ala2,D-Leu5,Lys6]enkephalin were readily dissociated by NaCl and Gpp(NH)p, producing negligible loss at 3 microM. This suggests that DALCE binds covalently to the receptors. Pretreatment of membranes with the reducing agents dithiothreitol and beta-mercaptoethanol had no effect on opiate binding. Thus, loss of sites required both specific recognition by opiate receptors and a thiol group. The irreversible effect of DALCE was completely selective for delta-receptors. Pretreatment with DALCE had no effect on binding of ligands to mu- or kappa-receptors. The effect of DALCE on delta-binding was: 1) markedly attenuated by inclusion of dithiothreitol in the preincubation buffer, 2) partially reversed by subsequent incubation with dithiothreitol, 3) slightly enhanced when converted to the disulfide-linked dimer, and 4) prevented by blocking the DALCE sulfhydryl group with N-ethylmaleimide or iodoacetamide. These results indicate that DALCE binds covalently to delta-receptors by forming a disulfide bond with a sulfhydryl group in the binding site. The mechanism may involve a thiol-disulfide exchange reaction.     

The effect of hypoxic hypoxia on the physicochemical and functional properties of hemoglobin in rats]

The effect of intermittent altitude chamber hypoxia is established to cause an increase in solvability of laboratory rat hemoglobin. Results of immunochemical and fluorescent analysis of the samples of hemoglobin and its component are presented and discussed. They prove that changes in solvability of hemoglobin are determined by the conformational reconstructions of the respiration protein as a result of formation of the complexes with internally erythrocytic metabolites.     

Protective effect of malonic acid in hypoxic hypoxia]

Malonic acid injection causes an increase in the survival of rats with acute hypoxic hypoxia. Endogenic malonic acid is supposed to be of great importance in stimulating tissue resistance to hypoxia.     

Terminal vascular bed of the connective tissue membrane in hypoxic hypoxia]

Morphological changes of all links of the terminal vascular bed during acute hypoxic hypoxia were studied in experiment and in postmortem material. A complex of methods was used including microdissection, injection with India ink - gelatin, clearing, silver nitrate impregnation after V. V. Kuprijanov, staining after Van Gieson and with hematoxylin-eosin, biomicroscopy and reoencephalography. Signs of desorganization of the vascular bed were revealed which manifested themselves as changes in microangioarchitectonics and diameters of vascular lumens, increased permiability of their walls with saturation of them with white and escape of its forming elements of the blood outside the limits of the vessels, as well as in destruction of the aggregate state of the blood. It considerably enlarges our knowledge of the state and changes in the vascular bed during hypoxic hypoxia.     

The hypoxia signaling pathway and hypoxic adaptation in fishes

The hypoxia signaling pathway is an evolutionarily conserved cellular signaling pathway present in animals ranging from Caenorhabditis elegans to mammals.The pathway is crucial for oxygen homeostasis maintenance.Hypoxia-inducible factors(HIF-1αand HIF-2α)are master regulators in the hypoxia signaling pathway.Oxygen concentrations vary a lot in the aquatic environment.To deal with this,fishes have adapted and developed varying strategies for living in hypoxic conditions.Investigations into the strategies and mechanisms of hypoxia adaptation in fishes will allow us to understand fish speciation and breed hypoxia-tolerant fish species/strains.This review summarizes the process of the hypoxia signaling pathway and its regulation,as well as the mechanism of hypoxia adaptation in fishes.     

Dynamics of changes in the cerebral and erythrocyte ATPase activity of rats with hypoxic hypoxia]

A long-term (for 3 hours) hypoxic hypoxia was accompanied in rats by wave changes of the brain tissue Na++K+-ATPase activity. This activity decreased after a 15-minute exposure; it increased after 2 hours and fell again after a 3-hour hypoxia (decompensation period). The membrane transport enzymes of erythrocytes proved to be more resistant to hypoxia than the brain cell enzymes.     

Manifestation of oxygen effect during normobaric hypoxic hypoxia in the intrauterine and postnatal developmental periods]

The experiments on rats have shown that hypoxic gas mixture containing 10% of oxygen and 90% of nitrogen (HGM-10) under normobaric conditions exerts a highly reliable radioprotective effect on progeny when 11-day pregnant animals are exposed to total irradiation (60Co, 20 Gy). As distinct from the known radioprotector, mexamine, (5-methoxytryptamine), HGM-10 has a pronounced radioprotective effect during the first days (1-5) after birth. Radioresistance of new-born rats correlates with the level of pO2 in the tissues which progressively decreases with respiration of HGM-10 and remains unchanged after mexamine (10 mg/kg) introduction.