Biological activity of cholecystokinin (30–33) tetrapeptide analogues

Analogues of the endogenous peptide corresponding to the 30–33 sequence of cholecystokinin (Trp-Met-Asp-Phe-NH₂) were synthesized, and their biological activity was studied. It was shown that, in rats, the N-succinylated Nle² analogue of this tetrapeptide exhibits increased anxiolytic properties in the dark-light chamber test and an enhanced alcohol intake by both the control animals and the alcohol-dependent animals under the conditions of free choice. Introduction of an isopropyl residue into the C-terminal amide of the Nle² analogue resulted in the appearance of anxiogenic and antialcohol activity and the ability to increase the morphine analgesic effect in the tail-flick test on rats. The two synthesized analogues retained an affinity for cholecystokinin receptors.__________Translated from Bioorganicheskaya Khimiya, Vol. 31, No. 2, 2005, pp. 130–139.Original Russian Text Copyright © 2005 by Proskuryakova, Bespalova, Palkeeva, Petrichenko, Pankratova, Shokhonova, Anokhina.     

Distribution of MT1 Melatonin Receptor Promoter-Driven RFP Expression in the Brains of BAC C3H/HeN Transgenic Mice

The pineal hormone melatonin activates two G-protein coupled receptors (MT₁ and MT₂) to regulate in part biological functions. The MT₁ and MT₂ melatonin receptors are heterogeneously distributed in the mammalian brain including humans. In the mouse, only a few reports have assessed the expression of the MT₁ melatonin receptor expression using 2-iodomelatonin binding, in situ hybridization and/or polymerase chain reaction (PCR). Here, we described a transgenic mouse in which red fluorescence protein (RFP) is expressed under the control of the endogenous MT₁ promoter, by inserting RFP cDNA at the start codon of MTNR1a gene within a bacterial artificial chromosome (BAC) and expressing this construct as a transgene. The expression of RFP in the brain of this mouse was examined either directly under a fluorescent microscope or immunohistochemically using an antibody against RFP (RFP-MT₁). RFP-MT₁ expression was observed in many brain regions including the subcommissural organ, parts of the ependyma lining the lateral and third ventricles, the aqueduct, the hippocampus, the cerebellum, the pars tuberalis, the habenula and the habenula commissure. This RFP-MT₁ transgenic model provides a unique tool for studying the distribution of the MT₁ receptor in the brain of mice, its cell-specific expression and its function in vivo.     

Molecular and Biochemical Aspects of Light Regulation of 2-Oxoglutarate Dehydrogenase in Plants

Russian Journal of Plant Physiology - Molecular and epigenetic mechanisms for regulation of a key TCA enzyme 2-oxoglutarate dehydrogenase (2-OGDH) were investigated in connection with plant...     

Vomeronasal/accessory olfactory system and pheromonal recognition

Pregnancy block in mice requires exposure of recently mated females to urinary pheromones of a strange male, and when working with inbred strains this invariably requires urine from an outbred line. The pheromones which induce oestrus and early puberty in mice have been identified as the brevicomins and dihydrothiazoles. Since the same vomeronasal, neural and neuroendocrine pathways are also activated in pregnancy block, these compounds are likely candidates for pregnancy blocking pheromones. However, these relatively simple chemicals lack the capacity to code for differing mouse strains. Since large quantities of the polymorphic major urinary proteins from the lipocalin family found in urine serve as transporters for the dihydrothiazoles and brevicomins, and differ across strains, then these proteins must participate in pheromone recognition in the context of pregnancy block.      

Immunomodulating and analgesic activity of synthetic fragments of various proteins and immunopeptides

The biological activity of certain new peptides synthesized by the classic methods of peptide chemistry is investigated. The characteristic feature of these peptides is that they are parts of the sequences of many naturally occurring proteins and immunopeptides (beta-lactoglobulin, vicilin, B-hordein, gamma-gliadin, histones, Thy-I-antigen, thymosin beta, leukocyte interferon, neutrophil peptides and others) tested by the computer methods. Most of the investigated peptides are shown to enhance E-rosette-forming activity of human T-lymphocytes and to possess the analgesic activity. In some cases the analgesic effect was antagonized by naloxone. The possible mechanism of appearance of such peptide fragments and their biological role in human organism is discussed.     

Brain catecholamines at the early stage of emotional stress

The blood pressure (BP) dynamics and catecholamine (CA) levels in the brain regions of August and Wistar rats were studied two hours after immobilization in order to elucidate the central neurochemical mechanisms leading to the destruction of BR self-regulation under emotional stress during the experiment. The BP level did not differ from the normal. The CA concentration in the hypothalamus, midbrain, isthmus rhombencephali and medulla oblongata underwent considerable changes. It is suggested that the mechanism of the CA changes in both strains of the rats exposed to stress is similar in the hypothalamus and medulla oblongata while both strains of the rats studied showed specificity in the activity of NA-synthesizing neurons of the isthmus rhombencephali and DA-synthesizing neurons of the midbrain that might be a cause of different resistance of cardiovascular functions during the later stage of immobilization.     

Effects of synthetic defensin fragments on aggregation and adhesion of epitheliolike cells

Normal course of processes of regeneration and epithelization of damaged tissues has been shown to be based on the capability of cells participating in these processes for selective adhesion. In the case of the complete or partial absence of this capability in the cells-participants of the wound healing process, the so-called non-healing wounds appear. In this connection, it remains actual to search for natural agents promoting healing of chronic non-healing wounds. In the present work, we studied effects of synthetic fragments of leukocytic antimicrobial peptides defensines—GER, FGER, and GERA—on aggregation and adhesion of epitheliolike cells of the CHO-K1 line. These peptides have been established to have aggregate-stimulating properties; besides, they enhance adhesion of the cells to the untreated plastic and inhibit fibronectinmediated cell adhesion. Possible pathways of regulation by peptides of processes of intercellular and cell-matrix interaction are discussed as well as ways of release of these compounds in an organism and their functional role in an organism.     

Homogeneity of the Biological Mechanisms of Individual Predispositions to the Abuse of Various Psychoactive Substances

The basic principles of the biological mechanisms of dependence on a psychoactive substance (PAS) are discussed. These mechanisms are the same when various PASs are used. They are mainly characterized by the specific changes in the dopamine (DA) neuromediation in the limbic regions of the brain. DA metabolism and the structural features of the dopamine receptor genes D2 and D4 were compared in patients with alcoholism with or without a family history of this disease. A comparison of findings with previously obtained experimental results and published data shows that the mechanisms of a predisposition to the abuse of various PASs are homogeneous and associated with specific genetic and functional features of the DA system.     

Genetic Control of Degradation of epsilon-Caprolactam,Toluene, and meta-Xylene in Pseudomonas putida Strain CT3

Microbiology - A bacterial strain CT3 with a unique ability to degrade anthropogenic toxic compounds ε-caprolactam, toluene, and meta-xylene as sole sources of carbon and energy was isolated...