Baclofen and γ-hydroxybutyrate: similar effects on cerebral dopamine neurones

Baclofen (20 mg/kg) caused an increase in the content of homovanillic acid (HVA) and dopamine (DA) in rat brain 2–3 h after drug injection without appreciable changes in the level of other monoamines and their main metabolites. Six and eight hours after baclofen, the content of HVA but not that of DA was reduced. Moreover, baclofen initially (20 min after injection) reduced, but later (105 min post drug) enhanced the accumulation of HVA induced by probenecid. The shortlasting (20 min) initial reduction of HVA elevation in probenecid-pretreated animals as well as the longlasting (6–8 h) decrease of HVA levels in rats injected with baclofen alone are interpreted to be due to a decreased release and metabolism of DA, probably as a consequence of the blockade of impulse flow in mesolimbic and nigro-striatal DA neurones. The increase in HVA and DA seen during the first few hours is thought to result from enhanced DA synthesis similar to that known for γ-hydroxybutyrate (GHB). This initial rise in HVA due to synthesis stimulation probably masked a reduction of HVA to be expected immediately after baclofen injection. The similarity between baclofen and GHB is stressed by the finding that baclofen counteracted the increase of HVA occuring after chlorpromazine and D-amphetamine but not that induced by the benzoquinolizine derivative, Ro 4-1284.     

Isolation of brain endopeptidases: influence of size and sequence of substrates structurally related to bradykinin.

Two thiol-activated endopeptidases with pH optima near pH 7.5 were isolated from the supernatant fraction of rabbit brain homogenates by DEAE-cellulose chromatography, gel filtration and isoelectrofocusing. Peptide bond hydrolysis was measured quantitatively by ion-exchange chromatography with an amino acid analyzer. Brain kininase A hydrolyzes the Phe5-Ser6 peptide bond in bradykinin (Bk), Arg1-Pro2-Pro3-Gly4-Phe5-Ser6-Pro7-Phe8-Arg9. It is isoelectric near pH 5.2 and has a molecular weight of approximately 71 000. The enzyme also hydrolyzes the Phe-Ser peptide bond in Lys-Bk, Met-Lys-Bk, des-Arg1-Bk, Lys9-Bk, Pro-Gly-Phe-Ser-Pro-Phe-Arg, and Gly-Pro-Phe-Ser-Pro-Phe-Arg, but does not hydrolyze (0.1%) this bond in des-Phe8-Arg9-Bk. Brain kininase B hydrolyzes the Pro7-Phe8 peptide bond in Bk. It is isoelectric at pH 4.9 and has a molecular weight of approximately 68 000. Brain kininase B also hydrolyzes the Pro-Phe bond in Lys-Bk, Met-Lys-Bk, Lys9-Bk, Ser-Pro-Phe-Arg, and Phe-Ser-Pro-Arg. Pretreatment of denatured kininogen with brain kininase A or B did not reduce the amount of trypsin-releasable Bk from this precursor protein, indicating that the Bk sequence, when part of a large protein, is not a substrate for either enzyme. However, kininase A and B hydrolyze the octadecapeptide Gly-Leu-Met-Lys-Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg-Ser-Val-Gin-Val. The data show that a large part of the C-terminal portion of bradykinin is important for the brain kininase A activity and, for both enzymes, the size of the peptide and presumably the residues adjacent to the scissle bond are important in determining the rate of peptide bond hydrolysis by these endopeptidases.     

THE EFFECT OF SULFHYDRYL REAGENTS ON THE TITYUSTOXIN-INDUCED ACETYLCHOLINE RELEASE IN RAT BRAIN SLICES1

Abstract— Pre-treatment of rat brain slices with organic mercurials prevents the increased acetylcholine release induced by tityustoxin. This inhibition is reversed by dithiothreitol. N-Ethylmaleimide blocks the tityustoxin effect irreversibly. Simultaneous incubation with mercurials and toxin reveals a competition of both ligands for a membrane sulfhydryl group apparently required for tityustoxin activity.     

On the fine structure of the electrocyte of Electrophorus electricus L.

Summary The general ultrastructure of the electrocyte, the basic unit of the electric organs of Electrophorus electricus, is analyzed. Presented herein are detailed observations of the syncytial surface, its fibrillar coat, invaginations of the plasma membrane and synaptic terminals. Using Thiéry's method glycogen granules were identified in the syncytial cytoplasm and inside the synaptic terminals, their size and structure being compatible with the muscular origin of the electric organs, to which the filamentous meshwork found in the cytoplasm may be related. Among the perinuclear-organelles, are dense bodies with crystalline patterns. The mitochondrial matrix contains dense granules, their size and structure varying according to the organ to which they belong and to the fixation method used.This work has been supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Conselho de Ensino para Graduados da UFRJ and Banco Nacional de Desenvolvimento Econômico, FUNTEC-241     

Xanthones from Tovomita pyrifolium

The wood of Tovomita pyrifolium (Guttiferae) contains the novel tovopyrifolins A [1,6-dihydroxy-7-methoxy-5-prenyl-6′,6′-dimethylpyrano (2′,3′:3,2)xanthone], B (1,5-dihydroxy-3,4-dimethoxyxanthone) and C (1,3,5-trihydroxy-2-methoxyxanthone) and also the known tovophyllins A and B [structure revised to 1,6-dihydroxy-5-prenyl-6′, 6′-dimethylpyrano(2′,3′:3,2)-6″,6″-dimethylpyrano(2″,3″:7,8)xanthone].     

Genome Sequences of Burkholderia sp. Strains CCGE1002 and H160, Isolated from Legume Nodules in Mexico and Brazil

The genome sequences of Burkholderia sp. strains CCGE1002 from Mexico and H160 from Brazil, isolated from legume nodules, are reported. Their gene contents in relation to plant-microbe interactions and xenobiotic degradation are discussed.     

Anti-inflammatory effect of l-cysteine (a semi-essential amino acid) on 5-FU-induced oral mucositis in hamsters

Oral mucositis is an inflammation of the oral mucosa mainly resulting from the cytotoxic effect of 5-fluorouracil (5-FU). The literature shows anti-inflammatory action of l-cysteine (l-cys) involving hydrogen sulfide (H₂S). In view of these properties, we investigate the effect of l-cys in oral mucositis induced by 5-FU in hamsters. The animals were divided into the following groups: saline 0.9%, mechanical trauma, 5-FU 60–40 mg/kg, l-cys 10/40 mg and NaHS 27 µg/kg. 5-FU was administered on days 1st to 2nd; 4th day excoriations were made on the mucosa; 5th–6th received l-cys and NaHS. For data analysis, histological analyses, mast cell count, inflammatory and antioxidants markers, and immunohistochemistry (cyclooxygenase-2(COX-2)/inducible nitric oxide synthase (iNOs)/H₂S) were performed. Results showed that l-cys decreased levels of inflammatory markers, mast cells, levels of COX-2, iNOS and increased levels of antioxidants markers and H₂S when compared to the group 5-FU (p < 0.005). It is suggested that l-cys increases the H₂S production with anti-inflammatory action in the 5-FU lesion.