Stimulation parameters determine role of GABAB receptors in long-term potentiation

Blockade of GABA_B receptors was reported to improve cognitive performance in mammals. The physiological basis of this effect is poorly understood. We investigated the effect of the GABA_B receptor antagonist CGP 35348 on long-term potentiation (LTP) in the CA1 area of the hippocampus in vitro and in vivo. In vitro the effect of CGP 35348 on LTP, induced either by two non-primed tetanic stimulations or by two primed bursts of stimuli, was investigated. In the presence of 1 mM CGP 35348 LTP was significantly facilitated following two non-primed tetanic trains, but was impaired following two primed burst stimulations. In vivo LTP was induced by applying non-primed trains of stimuli of increasing duration to the Schaffer collateral/commissural fibers. The potentiation of the population spike recorded in CA1 was significantly facilitated by CGP 35348 (100 mg/kg i.v.). In conclusion these findings demonstrate that the GABA_B antagonist CGP 35348 facilitates LTP in vitro and in vivo if induced by non-primed tetanic stimulation. In vitro, the mode of stimulation determines the effect of the GABA_B antagonist on LTP.     

Chemical analysis of the pheromone blends produced by males and females of the neotropical moth,Mocis megas (Guénée) (Lepidoptera,Noctuidae, Catocalinae)

Summary Pheromonal secretions produced by females and males of the noctuid moth,Mocis megas (Guénée) have been analyzed by gas chromatography and mass spectrometry (EI (electron impact) and CI (chemical ionization)). The female sex pheromone was a blend of (Z,Z,Z) 3,6,9 heneicosatriene (55%) and (Z,Z) 3,6-cis-9S, 10R-epoxyheneicosadiene (45%). Male secretion produced at the level of a prothoracic organ was a blend of two unsaturated major hydrocarbons: (Z,Z) 6,9 heneicosadiene, (64%) and (Z,Z,Z) 3,6,9 heneicosatriene (24%) and C₁₉, C₂₀ and C₂₂ homologues (total ratio 12%), as minor components. The trienic hydrocarbon was present in both sexes. The behavioral role of this male secretion has not yet been elucidated.     

Inhibition of TSH-stimulated thyroid hormone release and potentiation of TRH-stimulated TSH release by indomethacin in perifusion systems of rat thyroids and pituitaries

Summary Using indomethacin (Ind), a prostaglandin, synthesis inhibitor, in vivo experiments in rats and in vitro experiments with perifusion systems of rat thyroids and pituitaries were conducted. After 35 days of intragastric infusion of Ind, serum TSH levels were markedly increased, the thyroid was swollen and, as a consequence, T₃ and T₄ levels were normal. The T₃ release from perifused rat thyroids under continuous stimulation with 10 mU/ml TSH was inhibited significantly (p<0.01) by 1.0×10^–6 M Ind. On the other hand, the TSH release from perifused rat pituitaries under TRH stimulation was enhanced conspicuously by Ind. It was concluded that Ind decelerated thyroid hormone release from the thyroid and accelerated TSH release from the pituitary in perifusion systems.     

Supraphysiological dosages of vitamins and their implications in man

Summary Some recent evidence on the benefits and hazards of elevated dosages of vitamins is summarized. Special emphasis is given on the safety of vitamins A, D, K₁ and B₆. Furthermore, the possibly beneficial effects of vitamins for athletic performance as well as the preventive potential of antioxidative vitamins and of carotenoids against cancer are discussed.     

H2 receptor antagonists and human granulopoiesis

Summary The effect of 2 H₂ receptor antagonists (ranitidine and cimetidine) on the in vitro growth of human granulomonopoietic precursors (CFU-GM) was studied. Ranitidine, although having an anti H₂ receptor activity much greater than that of cimetidine, displays the same toxicity for CFU-GM.Acknowledgments. This work was supported by CNR, Rome, PFCCN and AIRC, Milan.     

The influence of N2-fixation on the carbon balance of leguminous plants

Biological dinitrogen fixation by legume-rhizobia symbiosis is very important both from the economic and from the ecological point of view. Theoretically, the reduction of the N₂-molecule to ammonia requires at least 16 ATP and 1.5 mg C per mg N fixed (N_fix). These values are difficult to determine in situ as this necessitates the determination of that part of root respiration which drives N₂-fixation. New approaches to such determinations and the results obtained are described. The values vary, depending on the plant species studied, the developmental stage of the plants and the genetic variability of macro- (and micro-?) symbionts. The values range between 1.5 and 4 mg C/mg N_fix. In some species (e.g.Vicia faba L. cv. Fribo), the apparent CO₂ assimilation is enhanced in order to meet this high energy need. In others (e.g.Pisum sativum L. cv. Grapis), root growth is restricted. Physiological criteria are discussed which allow an early diagnosis of the energetic efficiency of various combinations of macro-and microsymbionts as a basis for a selection in plant breeding.     

Role of phospholipids in the binding activity of vasoactive intestinal peptide receptors

Summary Phospholipase digestion of rat intestinal epithelial cell membranes was performed in order to study the influence of membrane phospholipids on the binding activity of VIP receptors. Phospholipases A₂ and C strougly (ED₅₀4×10^–2 and 4×10^–1 g/ml, respectively) and rapidly reduced¹²⁵I-VIP binding to membranes whereas phospholipase D was ineffective. This suggests an important role of both hydrophobic and hydrophilic groups of phospholipids on VIP receptor binding activity.This work was supported by INSERM (CRL 827017) and the Fondation pour la Recherche Médicale Française.     

Adult hippocampal neurogenesis: regulation by HIV and drugs of abuse

New dentate granule cells are continuously generated from neural progenitor cells and integrated into the existing hippocampal circuitry in the adult mammalian brain through an orchestrated process termed adult neurogenesis. While the exact function remains elusive, adult neurogenesis has been suggested to play important roles in specific cognitive functions. Adult hippocampal neurogenesis is regulated by a variety of physiological and pathological stimulations. Here we review emerging evidence showing that HIV infection and several drugs of abuse result in molecular changes that may affect different aspects of adult hippocampal neurogenesis. These new findings raise the possibility that cognitive dysfunction in the setting of HIV infection or drug abuse may, in part, be related to alterations in hippocampal neurogenesis. A better understanding of how HIV and drugs of abuse affect both molecular and cellular aspects of adult neurogenesis may lead to development of more effective therapeutic interventions for these interlinked epidemics. Received 6 February 2007; received after revision 26 March 2007; accepted 25 April 2007     

Loss of antibody production accompanied by chromosome loss in a cloned hybrid line secreting antibodies to sheep red blood cells

Summary Somatic cell hybrids between Sp2/O-Ag14 mouse myeloma cells and lymphocytes derived from BALB/c mice hyperimmunized with sheep red blood cells (SRBC) were produced. One hybrid producing IgG₁ antibody to SRBC was selected, cloned twice and subsequently transferred to BALB/c mice. After a number of transfers it was found that the antibody titer in ascitec fluid gradually decreased. Cytogenetic analysis revealed gradual chromosome loss in the hybrid clone, which produced progressively less antibody.     

Dogma and dreams: experimental lessons for epilepsy mechanism chasers

Epilepsy mechanism chasers face one major difficulty. Since we don’t know how the normal brain works, we can’t start to understand how the diseased brain fails. Most of today’s hypotheses are based on what we think about ‘normal’ brain function, which may lead to misconceptions, as will be developed here. Furthermore, since there are many different types of epilepsies, some mechanisms may only be relevant to some epilepsies. Here, I shall focus on temporal lobe epilepsy (TLE) the most common form of partial epilepsy in adults. TLE is often drug resistant, as are 30–40% of all forms of epilepsies. The failure of drug-treatments most likely reflects our lack of knowledge of the underlying mechanisms.Received 10 January 2005; received after revision 3 March 2005; accepted 23 March 2005     

Role of lysine side chains in metallothionein

Summary pK_a-Values of lysine residues of mammalian metallothionein were determined by chemical titration measurements of -CH₂ lysine resonances in the¹H-NMR spectra. They are about 0.5 pH-unit higher than the average pK_a-value of a metal-free derivative, suggesting interaction of the positively charged residues with the two three-fold negatively charged metal-thiolate clusters of the metal-containing form. Deprotonation of the lysines leads to circular dichroism changes attributable to an electrostatically induced structural transition of the protein.To whom correspondence concerning this paper should be addressed.     

Natural killer-like activity in human cultured lymphoid cells propagated in the presence of interleukin-2: acquired resistance to prostaglandin E2- or dexamethasone-mediated suppression

Summary The cytotoxic activity of human peripheral blood lymphocytes against the natural killer-sensitive target K562 was suppressed both by prostaglandin E₂ and dexamethasone. On the other hand, cultured lymphoid cells propagated in the presence of interleukin-2 showed strong cytotoxic reactivity against K562 targets, and were resistant to prostaglandin E₂- or dexamethasone-mediated suppression.     

4-Aminopyridine and barium chloride attenuate the anti-epileptic effect of carbamazepine in hippocampal slices

Summary The exact mode of action of the anti-epileptic agent carbamazepine is unknown. In hippocampal slices in which epileptiform discharges were induced by addition of penicillin to the perfusion medium, the depressant effect of carbamazepine was attenuated by the potassium-channel blockers barium chloride (0.1 mM) and 4-aminopyridine (200 M), which suggested that potassium fluxes might be involved in the mechanism of action of carbamazepine.     

Early-life undernutrition causes deficits in rat dentate gyrus granule cell number

Recently developed stereological methods have been used in experiments to examine the effects of two levels of undernutrition during early postnatal life on the total number of rat dentate gyrus granule cells. This study has shown that previously undernourished rats have significant deficits in the total number of this particular type of neuron.     

Influence of phosphorus supply and light intensity on mycorrhizal response inPisum-Rhizobium-Glomus symbiosis

The influence of mycorrhizal colonization withGlomus mosseae on parameters of N₂ fixation and plant growth was studied in pot experiments with pea plants (Pisum sativum L.) infected withRhizobium leguminosarum and supplied with varied levels of phosphorus (P) and nitrogen (N). Reduced light intensities were used to evaluate the dependence of the microsymbionts on assimilate supply. In plants grown with low P supply, mycorrhization increased the concentration of P in shoots, and thus N₂ fixation. Reduced light intensity significantly depressed mycorrhizal colonization and nodule growth in low-P plants. When P supply did not limit plant growth and N₂ fixation, however, the percentage of mycorrhizal colonization was reduced due to the higher P status, and the microsymbionts were not impaired by low light intensities. To maximize carbohydrate supply, another experiment was carried out at high light intensity of 900 mol m^–2s^–1 and with non-limiting P supply. Nitrogen fertilization, given as starter N, enhanced plant growth, but delayed nodule formation. Towards flowering, nodulation rapidly increased, but less so inGlomus inoculated plants. After 28 days mycorrhizal plants were lower in shoot dry weight, nodule dry weight and nitrogenase activity. The results suggest that under many, but not all, environmental conditions the host plant is able to restrict mycorrhizal colonization and, thus, to prevent impairment ofRhizobium symbiosis.deceased in May 1994     

Phosphate transport inClaviceps sp. strain SD-58

Summary Phosphate uptake inClaviceps sp. strain SD-58 was found to be linear for 20 min, proportional to cell density in mg/ml, energy dependent, and taking place against a concentration gradient with a K_m value of 45.45×10^–5 M. Osmotic shock treatment to the cell caused a reduction in phosphate uptake associated with the release of binding protein. Partial restoration of uptake was observed on incubation of osmotically shocked cells with shock fluid. The results are discussed with reference to the effect of phosphate on alkaloid synthesis inClaviceps sp. strain SD-58.     

Neurosteroid enhances glutamate release in rat prelimbic cortex via activation of α1-adrenergic and σ1 receptors

The present paper studied the effect and mechanism of neurosteroid pregnenolone sulfate (PREGS) on spontaneous glutamate release using electrophysiological and biochemical methods combined with a pharmacological approach. The results suggested that PREGS had a selective enhancing effect on spontaneous glutamate release in the prelimbic cortex and the hippocampus but not in the striatum. The effect of PREGS in the prelimbic cortex appeared to be via modulation of ₁-adrenergic and ₁ receptors, but in the hippocampus it might be dependent on ₁ receptors only. The activation of ₁-adrenergic receptors synergized ₁ receptor activation in the prelimbic cortex. Intracellular calcium released from the endoplasmic reticulum, protein kinase C, adenylyl cyclase and protein kinase A played a key role in the effect of PREGS. Intracellular calcium, protein kinase C and adenylyl cyclase might be upstream events in the activation of protein kinase A after PREGS.Received 7 January 2005; received after revision 19 February 2005; accepted 22 February 2005 Available online 29 March 2005     

Chitin synthetase activity and inhibition in different insect microsomal preparations

Summary To facilitate massive screening and for structure-activity relationship studies of chitin synthesis inhibitors, methods to obtain the chitin synthetase (CS) containing microsomal fraction from the postmitochondrial supernatant were examined. Compared with fractionation by differential centrifugation, the CaCl₂ precipitate yielded the most active CS preparation. Acidification (pH 5.6) and polyethylene glycol 8000 (5%) treatments resulted in relatively low CS activity. Inhibitory effects were detected with polyoxin-D and 1-geranyl-2-methyl benzimidazole, a novel CS inhibitor, but not with benzoylphenyl ureas.     

Specificity in the hydrolysis of N-acyl-L-phenylalanine 4-nitroanilides by chymotrypsin

Summary The affinity of N-acyl-L-phenylalanine 4-nitroanilides for chymotrypsin is enhanced as the hydrophobicity of non-amino acid residues in the P₂-position of the substrates increases, whereas k_cat remains nearly constant. On the other hand, if alanine or leucine is in the P₂-position k_cat increases with decreasing K_M.     

Zur Konstitution von Helvolinsäure und Cephalosporin P1

Summary On the basis of nuclear magnetic resonance measurements and in agreement with recently reported mass-spectrometric investigations it is shown that the molecular formulae of Helvolic acid and Cephalosporin P₁ must be revised to C₃₃H₄₄O₈ and C₃₃H₅₀O₈ respectively, and that the additional carbon atom is present as an angular methyl group.A comparison with the data obtained with fusidic acid points to a similarity among the three substances which is closer than hitherto suspected.