Naturally occurring compounds affect glutamatergic neurotransmission in rat brain.

Natural products, including those derived from plants, have largely contributed to the development of therapeutic drugs. Glutamate is the main excitatory neurotransmitter in the central nervous system and it is also considered a nociceptive neurotransmitter, by acting on peripheral nervous system. For this reason, in this study we investigated the effects of the hydroalcoholic extracts from Drymis winteri (polygodial and drimanial), Phyllanthus (rutin and quercetine), Jathopha elliptica (jatrophone), Hedyosmum brasiliense (13HDS), Ocotea suaveolens (Tormentic acid), Protium kleinii (alphabeta-amyrin), Citrus paradise (naringin), soybean (genistein) and Crataeva nurvala (lupeol), described as having antinociceptive effects, on glutamatergic transmission parameters, such as [(3)H]glutamate binding, [(3)H]glutamate uptake by synaptic vesicles and astrocyte cultures, and synaptosomal [(3)H]glutamate release. All the glutamatergic parameters were affected by one or more of these compounds. Specifically, drimanial and polygodial presented more broad and profound effects, requiring more investigation on their mechanisms. The putative central side effects of these compounds, via the glutamatergic system, are discussed.

The sesquiterpenes polygodial and drimanial in vitro affect glutamatergic transport in rat brain.

Natural products including those derived from plants, have over the years greatly contributed to the development of therapeutic drugs. Polygodial and drimanial are sesquiterpenes isolated from the bark of the plant Drymis Winteri (Winteraceae) that exhibit antinociceptive properties. Since peripheral glutamate presents nociceptive actions, in this study it was investigated the effects of hydroalcooholic extracts from Drymis winteri (polygodial and drimanial) on the glutamatergic system in rat brain. Polygodial and drimanial inhibited glutamate uptake by astrocytes, as well as by cortical, hippocampal and striatal slices, and increased synaptosomal glutamate release. These concurrent effects would predispose to an increase in the extracellular glutamate concentrations, leading to possible neurotoxic effects (excitotoxicity) of these natural compounds, which would suggest the need for some caution in their therapeutic application.

Amnesic effect of GMP depends on its conversion to guanosine.

Extracellular guanine-based purines, namely the nucleotides GTP, GDP, GMP and the nucleoside guanosine, exert important neuroprotective and neuromodulator roles in the central nervous system, which may be related to inhibition of the glutamatergic neurotransmission activity. In this study, we investigated GMP effects on mice inhibitory avoidance performance and the dependence on its conversion to guanosine for such effect, by using the ecto-5'-nucleotidase specific inhibitor AOPCP. We also investigated if this conversion occurs in the central nervous system or peripherally, and if guanosine and GMP affect nociception by the tail-flick test. I.p. GMP or guanosine (7.5 mg/kg) or i.c.v. GMP (480 nmol) pretraining administration was amnesic for the inhibitory avoidance task. I.c.v. AOPCP (1 nmol) administration completely reversed the amnesic effect of i.c.v. GMP, but not of i.p. GMP, indicating that peripheral conversion of GMP to guanosine is probably relevant to this effect. AOPCP alone did not interfere with the performance. Furthermore, tail-flick measurement was unaffected by i.p. GMP and guanosine, suggesting that the amnesic effect of both purines was not due to some antinociceptive effect against the footshock used in the task. All these data together, in accordance to those previously observed in studies involving glutamate uptake and seizures reinforce the idea that guanosine is the specific extracellular guanine-based purines effector and indicate that its conversion occurs not only in the central nervous system but also peripherally.

A laboratory class on metabolism for medical and nursing students

Num curso prático de bioquímica para alunos de enfermagem e medicina seräo realizadas determinaçöes de glicemia, corpos cetônicos sangüíneos (acetoacetato), concentraçäo de glicogênio hepático e síntese de corpos cetônicos em ratos alimentados e em ratos submetidos a um jejum de 24 ou 48 horas. O consumo de glicose e acetoacetato por fatias de córtex cerebral seräo também determinados. Este curso permite uma ampla discussäo das inter-relaçöes metabólicas que ocorrem entre diferentes órgäos e tecidos do organismo. Permite, também, discutir as situaçöes metabólicas que ocorrem no jejum, diabetes mellitus e dieta hipoglicídica. Estas aulas säo exeqüíveis num período de duas horas ou em dois períodos de duas horas e säo economicamente viáveis