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G Escames

Publications and source records attributed to G Escames.

25 records · Page 2Linked to original sources

Melatonin's role as an anticonvulsant and neuronal protector: experimental and clinical evidence.

The pineal gland classically has been considered as a vestigial and mystic organ. In the last decades, and with the incorporation of new methodologic procedures, it could be proved that it also has physiologic actions that vary depending on the level of the phylogenetic scale. Its best-known secretion, melatonin, has been related to many different actions, such as sleep promotion, control of biologic rhythms, hormonal inhibition, and an inhibiting action on central nervous system regulation mechanisms. In animal experimentation, there are papers even accepting an anticonvulsant effect. In humans, evidence is reduced to few experiences. In addition to this clinical experience, there is other evidence that clearly relates melatonin to convulsive phenomena. This relationship must be mediated by the following mechanisms attributed to melatonin: altered brain GABAergic neurotransmission, its known interaction with benzodiazepinic brain receptors, through tryptophan metabolite activity (kynurenine, kynurenic acid), or even by its efficacy as a free-radical scavenger.

Animals↗

Melatonin and vitamin E limit nitric oxide-induced lipid peroxidation in rat brain homogenates.

We have investigated the level of lipid peroxidation (LPO) in rat brain homogenates in the presence of nitric oxide (NO) which was released by the addition of sodium nitroprusside (SNP) and compared it with that induced by H2O2. We also examined the effect of melatonin and vitamin E on the NO-induced LPO. The concentration of malonaldehyde (MDA) plus 4-hydroxyalkenals (4-HDA) was used as an index of LPO. While both H2O2 and SNP increased MDA + 4-HDA production in brain homogenates in a concentration-dependent manner, SNP was more potent than H2O2 at all concentrations tested. Both melatonin or vitamin E reduced NO-induced LPO in a dose-dependent manner in concentrations ranging from 10 microM to 10 mM. Under the in vitro conditions of this experiment, vitamin E was more efficient than melatonin in limiting NO-induced LPO in rat brain homogenates.

Animals↗

Melatonin prevents changes in microsomal membrane fluidity during induced lipid peroxidation.

We tested the effect of melatonin on membrane fluidity in microsomes of a rat liver model in which lipid peroxidation was induced by the addition of FeCl3, ADP and NADPH. Membrane fluidity was monitored using fluorescence spectroscopy and lipid peroxidation was estimated by quantifying malonaldehyde (MDA)+4-hydroxyalkenals (4-HDA) concentrations following the induction of lipid peroxidation with and without pre-incubation with melatonin (1 microM-3 mM). Membrane rigidity increased during induced lipid peroxidation while melatonin reduced in a concentration-dependent manner both membrane rigidity and MDA+4-HDA generation. Melatonin's protective effect may relate to its known ability to scavenge free radicals and function as an antioxidant.

Adenosine Diphosphate↗

Melatonin-dopamine interaction in the striatal projection area of sensorimotor cortex in the rat.

The excitatory response to motor cortex stimulation of 201 striatal neurones was recorded electrophysiologically to test the effects of melatonin (aMT) and/or D1 and D2 antagonists. Iontophoresis of aMT attenuated the excitatory response in 68.5% of neurones, with a latency of 2-4 min and enhanced the excitatory response in 11.9% of the neurones; 19.6% showed no change in response. Iontophoresis of sulpiride (D2 antagonist) produced an immediate increase in the excitatory response in 62.8% of neurones, an attenuation in 2.3% and no change in the response of 34.9%. The ejection of sulpiride counteracted the aMT-dependent inhibition of the excitatory response of striatal neurones. SCH-23390 (D1 antagonist) iontophoresis had no significant effect. The results show that the same striatal units may be driven by aMT and D2 receptors. However, the significant difference in the latency of the responses suggests that the effects of these two substances are mediated by different receptor/intracellular messengers.

Animals↗

Participation of ACTH1-10 and ACTH4-10 on the melatonin modulation of benzodiazepine receptors in rat cerebral cortex.

In this study, we examined the effect of intracerebroventricular (i.c.v) injection of melatonin and/or ACTH1-10 and ACTH4-10 on [3H]flunitrazepam binding sites in the cerebral cortex of hypophysectomized rats. Hypophysectomy increased the Bmax (maximum number of binding sites) of benzodiazepine (BNZ) receptors for at least 7 days after surgery, without changing KD (dissociation constant). The i.c.v. injection of melatonin to hypophysectomized rats significantly increased Bmax, whereas the same doses of melatonin were ineffective in sham-operated animals. In both cases, KD values were unchanged. The i.c.v. injection of ACTH1-10 to hypophysectomized animals significantly increased Bmax, an effect that was enhanced by simultaneous i.c.v. injection of ACTH1-10 + melatonin, reaching higher values of Bmax than the i.c.v. injection of these hormones individually. No significant changes in KD values were found after ACTH1-10 and/or melatonin administration. However, the i.c.v. injection of ACTH4-10 to hypophysectomized rats did not change Bmax, although it significantly increased KD values, indicating a decrease in the BNZ binding affinity. Melatonin injection counteracted this effect of ACTH4-10, returning KD to the control value. Moreover, although the lower dose of i.c.v. melatonin used, 10 ng, was unable to modify Bmax of BNZ binding in the ACTH4-10-injected group, the higher dose, 20 ng, significantly increased Bmax. The results suggest that these ACTH-derived peptides can modulate the effect of melatonin on brain benzodiazepine receptors.

Adrenocorticotropic Hormone↗

Cell protective role of melatonin in the brain.

In recent years an increasing amount of data has been published involving melatonin in the control of brain function. The pineal gland exerts a depressive influence on CNS excitability. This activity is linked to melatonin, since pharmacological doses of the hormone prevent seizures in several animal models. In addition, melatonin also has analgesic properties in these species. However, the sites and mechanism of melatonin action are not known. A role for the pineal gland and its hormone melatonin as a homeostatic system controlling brain excitability has been proposed, and GABA-containing neurons may be involved in some central action of melatonin. There is evidence supporting a role of melatonin in the regulation of the GABA-benzodiazepine receptor complex, and it appears that melatonin potentiates this inhibitory neurotransmitter system in brain. Melatonin does not bind to GABA or benzodiazepine binding sites themselves, because in vitro binding data showed that melatonin is a weak competitor of benzodiazepine binding in brain membranes at concentrations greater than 10(-5) M. The effect of melatonin on brain activity also involves the participation of corticotropic and opioid peptides, and the existence of an opioid-antiopioid homeostatic system is proposed, with the GABA-benzodiazepine receptor complex as an effector. Moreover, the interaction of melatonin with corticotropic peptides and mitochondrial benzodiazepine receptors may result in a participation of neurosteroids in the control of GABA activity and function. The most recently available data from biochemical and electrophysiological studies support the possibility that the anticonvulsant and depressive effects of melatonin on neuron activity may depend on its antioxidant and antiexcitotoxic roles, acting as a free radical scavenger and regulating brain glutamate receptors. The full characterization of the nuclear melatonin receptor explains the genomic effects of melatonin, opening a new perspective regarding actions and roles of melatonin as a cellular protector.

Animals↗