Subject(s)
Analgesics, Opioid/metabolism , Opioid Peptides/metabolism , Peptide Fragments/metabolism , Receptors, Opioid/metabolism , Tritium/metabolism , Amino Acid Sequence , Analgesics, Opioid/chemistry , Animals , Brain/metabolism , Opioid Peptides/chemistry , Opioid Peptides/genetics , Peptide Fragments/chemistry , Peptide Fragments/genetics , Rats , Tritium/chemistryABSTRACT
Peptide anxiolytic selank (Thr-Lys-Pro-Arg-Pro-Gly-Pro) applied intraperitoneally in doses of 0.01, 0.1, 1.0, and 10.0 mg/kg to mice reduces behavioral manifestations of dopaminergic system induced by apomorphine in the verticalization test. This effect was comparable to that of atypical antipsychotic olanzapine in near-therapeutic doses (0.1 and 1.0 mg/kg, intraperitoneally) and was blocked with nonselective opioid receptor antagonist naloxone (10 mg/kg, intraperitoneally). Radioreceptor assay showed that selank did not displace nonselective D2-dopamine receptor antagonist (3)H-spiperone (EC50>100 microM) and delta- and micro-opioid receptor ligand 3H-DADLE (EC50>40 microM) from specific binding sites on rat brain membranes. It is hypothesized that the revealed behavioral effect of selank is mediated by its modulating effect on the endogenous opioid system and specifically, by its effect on activity of enkephalin-degrading enzymes.
Subject(s)
Anti-Anxiety Agents/pharmacology , Apomorphine/pharmacology , Behavior, Animal/drug effects , Dopamine/physiology , Naloxone/pharmacology , Oligopeptides/pharmacology , Animals , Benzodiazepines/pharmacology , Enkephalin, Leucine-2-Alanine/metabolism , Male , Mice , Olanzapine , Oligopeptides/antagonists & inhibitors , Oligopeptides/metabolism , Receptors, Dopamine D2/metabolism , Receptors, Opioid, mu/metabolism , Spiperone/metabolism , Stereotyped Behavior/drug effectsABSTRACT
Radioreceptor analysis showed that human beta-casomorphin-7 displaced 3H-spiperone from 5-HT2-serotonin receptors of the rat cerebral frontal cortex: EC50 8 +/- 1 microM. Human and bovine beta-casomorphin-7 dose-dependently blocked serotonin-induced human platelet aggregation: IC50 5 +/- 1 and 20 +/- 4 microM, respectively. It was proved that beta-casomorphins-7 act as 5-HT2-serotonin receptor antagonists; one of the mechanisms of their biological effects is presumably associated with modulation of the serotoninergic system.
Subject(s)
Endorphins/metabolism , Peptide Fragments/metabolism , Receptors, Serotonin, 5-HT2/metabolism , Animals , Cattle , Cerebral Cortex/drug effects , Dopamine Antagonists/pharmacology , Dose-Response Relationship, Drug , Humans , Inhibitory Concentration 50 , Ketanserin/pharmacology , Platelet Aggregation , Protein Binding , Rats , Serotonin Antagonists/pharmacology , Spiperone/pharmacologyABSTRACT
The half-life of leu-enkephalin in the serum of infants aged under 1 year is significantly shorter than in adults. In girls leu-enkephalin half-life is significantly longer than in boys. The half-life of leu-enkephalin is different in infants on breast and formula feeding. Nine characteristics of temperament in infants of the first year of life were determined using EITQ and ITQ questionnaires. Serum leu-enkephalin half-life directly correlated with temperament characteristics (activity, perception, threshold), but not with the level psychomotor development.
Subject(s)
Breast Feeding , Enkephalin, Leucine/blood , Infant Formula , Temperament , Adult , Female , Half-Life , Humans , Infant , Male , Surveys and QuestionnairesABSTRACT
Comparative study of plasma activities of enkephalin-degrading enzymes in mice with different phenotypes of emotional and stress reactions revealed significant differences between intact BALB/c and C57Bl/6 mice by the half-life of plasma leu-enkephalin. Selank in a dose of 100 micrograms/kg produced an anxiolytic effect in the open-field test and increased the half-life of plasma leu-enkephalin in BALB/c mice, but had no effect on behavioral reactions and enkephalinase activities in C57Bl/6 mice. Our results suggest that anxiolytic activity of Selank is associated with inhibition of enkephalin-degrading enzymes.
Subject(s)
Anti-Anxiety Agents/pharmacology , Motor Activity/drug effects , Neprilysin/blood , Oligopeptides/pharmacology , Stress, Physiological/physiopathology , Animals , Enkephalin, Leucine/metabolism , Humans , Male , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Phenotype , Stress, Physiological/metabolismABSTRACT
Examination of patients with various forms of anxiety and phobic disorders (according to DSM-4 criteria) demonstrated a considerable shortening of enkephalin half-life and reduced total enkephalinase activity in the blood during generalized anxiety, but not during panic disorders and agoraphobia. This was probably related to low blood concentration of endogenous inhibitors of enkephalin-degrading enzymes in patients with generalized anxiety disorders. Heptapeptide Selank (Thr-Lys-Pro-Arg-Pro-Gly-Pro), which attenuates behavioral anxiety reactions and does not cause side effects typical of most anxiolytics, dose-dependently inhibited enzymatic hydrolysis of plasma enkephalin (IC50 15 microM). Selank was more potent than peptidase inhibitors bacitracin and puromycin in inhibiting enkephalinases. These results suggest that high efficiency of Selank in the therapy of anxiety and phobic disorders, including generalized anxiety, is due to its ability to inhibit enkephalin hydrolysis.
Subject(s)
Anti-Anxiety Agents/pharmacology , Enkephalins/metabolism , Neurotic Disorders/drug therapy , Oligopeptides/pharmacology , Phobic Disorders/drug therapy , Anti-Anxiety Agents/therapeutic use , Humans , Neprilysin/antagonists & inhibitors , Neprilysin/metabolism , Neurotic Disorders/metabolism , Oligopeptides/therapeutic use , Phobic Disorders/metabolismABSTRACT
The purpose of this study was to evaluate mu- and delta-opioid receptors (OR) on human and murine dendritic cells (DC). Expression of mu- and delta-OR mRNA on DC was demonstrated by RT-PCR. The immunocytochemical and Western blot analyses revealed the expression of OR protein in DC. Radioreceptor assay demonstrated the specific saturated temperature-dependent binding of [3H]-labeled opioid ligand on DC and B(max)=2.8+/-0.3 fmol/10(6) cells and K(D)=4.8+/-1.0 nM were calculated by a Scatchard analysis. Finally, OR ligands DADLE and DAGO dose-dependently modulated the capacity of DC to induce T cell proliferation in an MLR assay. Importantly, expression of functional OR on DC was significantly increased upon TNF-alpha-induced DC maturation. Thus, these data suggest a new mechanism of opioid-dependent neuroendocrine immunomodulation.
Subject(s)
Dendritic Cells/chemistry , Receptors, Opioid, delta/analysis , Receptors, Opioid, mu/analysis , Animals , Cells, Cultured , Humans , Immunohistochemistry , Male , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , RNA, Messenger/analysis , Receptors, Opioid, delta/genetics , Receptors, Opioid, delta/physiology , Receptors, Opioid, mu/genetics , Receptors, Opioid, mu/physiology , Tumor Necrosis Factor-alpha/pharmacologySubject(s)
Dendritic Cells/physiology , Receptors, Opioid, delta/genetics , Animals , Bone Marrow Cells/cytology , Bone Marrow Cells/drug effects , Bone Marrow Cells/immunology , Cells, Cultured , Dendritic Cells/cytology , Dendritic Cells/drug effects , Enkephalin, Leucine-2-Alanine/pharmacology , Lymphocyte Activation , Male , Mice , Mice, Inbred C57BL , Receptors, Opioid, delta/physiology , Reverse Transcriptase Polymerase Chain Reaction , T-Lymphocytes/immunology , Tumor Necrosis Factor-alpha/pharmacologyABSTRACT
Frequency-resolved optical gating is used to characterize the propagation of intense femtosecond pulses in a nonlinear, dispersive medium. The combined effects of diffraction, normal dispersion, and cubic nonlinearity lead to pulse splitting. The role of the phase of the input pulse is studied. The results are compared with the predictions of a three-dimensional nonlinear Schrödinger equation.
ABSTRACT
The shape of two-dimensional solitary beams propagating in photorefractive media with an externally applied field is studied. The analytical results indicate that, for both focusing and defocusing nonlinearities, radially symmetric self-channeled beams do not exist. Some recent experiments are interpreted in light of the present results.
ABSTRACT
We consider nonstationary self-focusing of an optical beam propagating in a photorefractive medium in the framework of a two-dimensional model.
ABSTRACT
Stationary states of the system of two coupled double phase-conjugate mirrors are considered by taking into account small but finite seed values of the scattered waves at the entry into a nonlinear medium. Seed values are shown to determine both the possibility of self-starting oscillation for a given level of nonlinearity and the position and width of the bistability region.
ABSTRACT
The double phase-conjugate mirror is an oscillator in the framework of the one-dimensional theoretical model previously used for its description. Results of a more consistent two-dimensional approach qualitatively differ from those of a one-dimensional analysis, indicating that the double phase-conjugate mirror is a convective amplifier. The correct physical picture of the scattering development is revealed, and the transverse profiles of scattered beams and the dynamics of nonlinear reflectivity are calculated.
ABSTRACT
A reflection-grating self-pumped passive ring mirror is experimentally fabricated in a photorefractive KNbO(3) crystal. The observed values of nonlinear reflectivity are as much as 50%, and the response time of the mirror is several milliseconds.
ABSTRACT
The substances displacing labelled ligands from opiate receptors of the rat brain membrane fraction were found in the thymosin fraction 3 and acetoacid extract of the thymus by the radioreceptor assay. Comparison of the displacing activity of acetoacid extracts of perfused and non-perfused thymus and peripheral blood as well as an estimation of the blood content in the thymus allowed to conclude that blood does not participate in the ability of thymus preparations to bind to opiate receptors. On the basis of the enzymatic treatment data one can conclude that opiate receptor ligands present in thymus preparations are of peptide nature. The value of their sodium shift suggests that those peptides are partial agonists of morphine. The possible role of opioid peptides in the thymic endocrine function is discussed.
