Search PubMed⌕ Search

Biomedical subjects

A Machado

Publications and source records attributed to A Machado.

At least 19 recordsLinked to original sources
PubMed1992

Fast sodium channel dependency of the somatodendritic release of dopamine in the rat's brain.

Somatodendritic release of dopamine (DA) was studied by microdialysis. The basal release of endogenous extracellular DA in the rat's substantia nigra was 1.0 +/- 0.14 fmol/min (mean +/- S.E.M.; n = 6). Compared with the basal extracellular level of DA found in the striatum (12.9 +/- 0.94; n = 12), the former value was about 13 times smaller than the latter value. The addition to the Ringer solution of the fast sodium channel inhibitor, tetrodotoxin (TTX), at a concentration of 1 microM, produced the total disappearance of DA in the substantia nigra. When TTX was removed from the Ringer solution, the DA extracellular level came back slowly to the control value. This result suggests that the somatodendritic basal endogenous DA release measured by microdialysis is dependent on the sodium channel conductance.

Animals↗
PubMed1992

In vivo protection of striatum from MPP+ neurotoxicity by N-methyl-D-aspartate antagonists.

The present study was designed to assess by microdialysis whether N-methyl-D-aspartate (NMDA) non-competitive receptor antagonist, MK-801, is able to protect dopaminergic neurons against 1-methyl-4-phenylpyridinium ion (MPP+) neurotoxicity. An intraperitoneal injection of MK-801, 10 mumol/kg, half an hour before striatal MPP+, 10 mM, perfusion did not protect against its neurotoxicity. Afterwards, rats received an intraperitoneal injection of MK-801 every 4 h, during 24 h. Under these conditions, one day after MPP+ perfusion, DA basal extracellular levels were close to the detection limit of our HPLC equipment in both control and MK-801 treated rats. 3,4-Dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) basal output were lower in the former than in the latter rats. A second MPP+ perfusion statistically increased extracellular levels of DA and decreased DOPAC and HVA output in both groups of rats. However, the increase in extracellular DA overflow was higher in MK-801 treated rats than in the control group, indicating a higher number of surviving dopaminergic terminals. These results suggest that MK-801 is not able to protect against the primary direct neurotoxic action of MPP+, but a second MPP+ neurotoxic action mediated by excitatory amino acids could be partially prevented by MK-801.

1-Methyl-4-phenylpyridinium↗
PubMed1992

Effects of neonatal enucleation on catecholamine and serotonin turnover and amino acid levels in lateral geniculate nucleus and visual cortex of the adult rat.

Changes in turnover of dopamine (DA), noradrenaline (NA) and serotonin (5-hydroxytryptamine (5-HT)) and their metabolites, together with amino acid content, have been studied in dorsal lateral geniculate nucleus (LGNd) and visual cortex (VC) of neonatal enucleated rats. Enucleation increases the 5-HT turnover in LGNd and catecholamine turnover in VC. In contrast, enucleation decreases glutamate (and/or aspartate) content in LGNd and gamma-aminobutyric acid (GABA) in VC. These changes suggest an increase of the inhibitory action of the biogenic amines in LGNd after neonatal enucleation. The decrease of GABA in VC may reflect the importance of GABA in intracortical circuitry.

Amino Acids↗
PubMed1992

Changes in neurotransmitter levels associated with the deficiency of some essential amino acids in the diet.

The contents of dopamine (DA) and serotonin (5-HT) and their metabolites were measured in rat substantia nigra and corpus striatum following dietary changes, including restriction of protein content (low-protein diet; LPD) and the contents of several large neutral amino acids (isoleucine, leucine, methionine, phenylalanine, tryptophan and valine) for 25 d. The LPD produced an increase in the concentration of tyrosine (TYR) in the two regions of the brain studied. This effect was also observed with all amino acid deficiencies studied except for valine in the substantia nigra, tryptophan in the striatum and phenylalanine in both regions. Likewise, the concentration of 5-hydroxyindoleacetic acid (5-HIAA), the main metabolite of 5-HT, increased in the substantia nigra but not in the striatum after LPD, as well as with all the amino acid deficiencies studied, with the exception of tryptophan deficiency. In this case there was a dramatic effect on all components of the serotoninergic system, with decreases in the concentration of tryptophan (TRP; precursor), 5-HT and 5-HIAA. This behaviour clearly shows an interrelationship between precursor (TRP) availability and 5-HT synthesis and metabolism. With valine deficiency, dopaminergic and serotoninergic systems demonstrated opposite effects in the substantia nigra and the corpus striatum, and the behaviour of the two monoamines was also opposite within each structure. The significance of these changes is discussed.

Amino Acids, Essential↗
PubMed1992

Heterogeneity in the allosteric interaction between the gamma-aminobutyric acid (GABA) binding site and three different benzodiazepine binding sites of the GABAA/benzodiazepine receptor complex in the rat nervous system.

In the present communication we have investigated the allosteric coupling between the gamma-aminobutyric acidA (GABAA) receptor and the pharmacologically different benzodiazepine (BZD) receptor subtypes in membranes from various rat nervous system regions. Two types of BZD receptors (type I and type II) have been classically defined using CL 218.872. However, using zolpidem, three different BZD receptors have been identified by binding displacement experiments in membranes. These BZD receptor subtypes displayed high, low, and very low affinity for zolpidem. The distribution of the high- and low-affinity binding sites for zolpidem was similar to that of type I and type II subtypes in cerebellum, prefrontal cortex, and adult cerebral cortex. On the other hand, the very-low-affinity binding site was localized in relative high proportion in spinal cord, hippocampus, and newborn cerebral cortex and, to a minor extent, in superior colliculus. The allosteric coupling between the GABAA receptor and the BZD receptor subtypes was different. The high- and low-affinity binding sites for zolpidem seemed to have a similar high degree of coupling, except in spinal cord. On the other hand, the very-low-affinity binding site for zolpidem displayed a low degree of coupling with the GABAA receptor. These results seem to indicate that the different efficacy of GABA in enhancing the [3H]flunitrazepam binding could be due to the different BZD receptor subtypes present in the GABAA/BZD receptor complex and, moreover, led us to speculate that the low GABA efficacy found in membranes from spinal cord, hippocampus, and newborn cerebral cortex might be due to the presence in relatively high proportion of the very-low-affinity binding site for zolpidem.

Allosteric Site↗
PubMed1992

Changes in the turnover of monoamines in prefrontal cortex of rats fed on vitamin E-deficient diet.

Turnover of noradrenaline (NA), dopamine (DA), serotonin (5-HT), and their metabolites has been measured after a 15-day vitamin E-deficient diet in adult rat prefrontal cortex. Turnover rates of 3,4-dihydroxyphenylacetic acid, homovanillic acid, and 5-hydroxy-3-indoleacetic acid have been assayed from the disappearance rates after blocking by pargyline inhibition of monoamine oxidase. NA, DA, and 5-HT turnover rates have been measured as accumulation rates of NA, DA, and 5-HT after pargyline inhibition of monoamine oxidase. No change was found in the turnover rate of NA between control and experimental animals. In contrast, turnover rates of DA and homovanillic acid significantly increased in the animals fed on a low-vitamin E diet. However, the most striking results were found on the serotoninergic system. Levels of 5-HT and its main metabolite, 5-hydroxy-3-indoleacetic acid, and their respective turnover rates were lower in the vitamin E-deficient diet. These results could indicate that vitamin E is necessary for the normal functioning of the serotoninergic neurons in the rat prefrontal cortex. The involvement of vitamin E in preventing the formation of free radicals is well known. Therefore, this lack of protective effect after a 15-day vitamin E-deficient diet could be responsible for the neuronal damage to the serotoninergic system. The opposing results found in DA (increase) and 5-HT (decrease) turnover could provide further evidence for an inhibitory control of the serotoninergic ascending pathways to the dopaminergic system in the prefrontal cortex.

Animals↗
PubMed1992

Behavioral variability and frequency-dependent selection.

In Experiment 1, two conditions were compared: (a) a variability schedule in which food reinforcement was delivered for the fourth peck in a sequence that differed from the preceding N four-peck sequences, with the value of N continuously adjusted to maintain reinforcement probability approximately constant; and (b) a control condition in which the variability constraint was dropped but reinforcement probability remained constant. Pigeons responded approximately randomly under the variability schedule but showed strong stereotyped behavior under the control condition. Experiments 2 and 3 tested the idea that variability is the outcome of a type of frequency-dependent selection, namely differential reinforcement of infrequent behavior patterns. The results showed that pigeons alternate when frequency-dependent selection is applied to single pecks because alternation is an easy-to-learn stable pattern that satisfies the frequency-dependent condition. Nevertheless, 2 of 4 pigeons showed random behavior when frequency-dependent selection was applied to two pecks, even though double alternation is a permissible and stable stereotype under these conditions. It appears that random behavior results when pigeons are unable to acquire the stable stereotyped behavior under a given frequency-dependent schedule.

Animals↗
PubMed1992

[Peranal ulcers caused by ergotamine-containing suppositories].

Perianal ulcerations caused by suppositories application is an exceptional situation. We describe a 64 years old female with recurrent painless perianal ulcerations evoluting from 14 months. She medicates herself daily, since 8 to 10 years, with ergotamine tartarate suppositories, for the treatment of migraine. The diagnosis of ulcerated cutaneous drug reaction induced by ergotamine tartarate was confirmed by the complete healing of the lesions after stopping this medication and by their recurrence after the reintroduction of the treatment. These ulcerations are probably due to vasospasm of regional arterioles.

Anus Diseases↗
PubMed1991

Age effects on monoamine turnover of the rat substantia nigra.

Measurement of turnover of dopamine (DA), noradrenaline (NA) and serotonin (5-hydroxytryptamine (5-HT), and their metabolites has been performed in 6- and 24-month-old rats. Dopamine synthesis in 24-month-old rats did not show any change with respect to 6-month-old rats. However, our results seem to indicate decreased DA release in 24-month-old rats. This hypothesis could be supported by the changes found in the 3-methoxytyramine (3-MT) accumulation rate after monoamine oxidase inhibition with pargyline. The turnover of NA and its main metabolite, 3-methoxy-4-hydroxyphenylglycol (MHPG) decreased in 24-month-old rats compared with 6-month-old rats. Serotonin synthesis did not change in 24-month-old rats with respect to 6-month-old rats. However, the metabolism of 5-HT quantified as turnover of 5-hydroxy-3-indoleacetic acid (5-HIAA) increased in 24-month-old rats with respect to 6-month-old rats. The monoamine oxidase B:monoamine oxidase-A ratio increased in 24-month-old rats. The significance of these changes is discussed.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1991

Implication of lysine residues in the loss of 6-phosphogluconate dehydrogenase activity in aging human erythrocytes.

The activity of 6-phosphogluconate dehydrogenase (6-PGDH) decreases in aged human erythrocyte populations. The aged enzyme has 11 lysine residues less than the young enzyme, when they are measured with 2,4,6-trinitro-benzenesulfonic acid (TNBS). Treatment of young enzyme with ascorbate for 15 min produces the loss of 8 lysine residues and the diminution of enzymatic activity. These results suggest that there is a modification of lysine residue in human erythrocytes during senescence, probably caused by oxidation. This modification of lysine residue could imply the loss of enzymatic activity. This result is similar to that found in rat liver 6-PGDH during aging, described previously (Gordillo et al., J. Biol. Chem. 264 (1989) 17014-17019).

Adult↗
PubMed1991

The role of NADPH in the regulation of glucose-6-phosphate and 6-phosphogluconate dehydrogenases in rat adipose tissue.

Previous studies examining the regulation of the synthesis of G6PDH and 6PGDH in rat liver and adipose tissue have focused on the induction of these enzymes by different diets and some hormones. In rat liver these enzymatic activities seem to be regulated by a mechanism involving changes in the NADPH requirements. In this paper we have studied the effect of changes in the flux through different NADPH-consuming pathways on G6PDH and 6PGDH levels in adipose tissue and on the NADPH/NADP ratio. The results show that: I) an increase in the consumption of NADPH, caused by the activation of either fatty acid synthesis or detoxification systems which consume NADPH, is paralleled by an increase in the levels of these enzymes; II) when the increase in consumption of NADPH is prevented, the G6PDH and 6PGDH levels do not change.

Adipose Tissue↗
PubMed1991

Involvement of diminution of glutathione, produced by deficiency of methionine in the diet, in the elevation of malic enzyme level in rat liver.

Rats fed on a low protein diet show an increase in the specific activity of malic enzyme and a concomitant decrease of glutathione concentration. We have studied the effect on malic enzyme activity of supplementing of low protein diet with essential amino acids. Only when methionine was excluded from the diet did the specific activity of malic enzyme increase to the same extent as found in rats fed with low protein diet. Immunoprecipitation of malic enzyme indicated that specific activity changes are the result of changes in the amounts of enzyme. Under all dietary conditions studied, the increase in malic enzyme activity is associated with a decrease in the concentration of GSH. To evaluate the possible causative role of GSH in malic enzyme induction, the specific activity of malic enzyme was measured in rats treated with BSO, an inhibitor of GSH biosynthesis. The results show that in BSO-treated rats the decrease of GSH levels is also accompanied by an increase in the activity of malic enzyme.

Amino Acids, Essential↗
PubMed1991

Age-dependent changes in the activity and isoenzymatic pattern of the phosphofructokinase in different areas of the central nervous systems.

Regional activity of phosphofructokinase enzyme and the amount of the isoenzyme C in 7 areas of young, adult and aged rats brain have been studied. The phosphofructokinase activity in substantia nigra decreased in adult and aged rats, but the maximum decrease was found in the septum of aged rats. There is a regional distribution of the isoenzyme C in the different areas studied. There was a general decrease in the amount of this isoenzyme in the areas studied with the exception of the hippocampus and the amygdala. The highest decrease was found in the septal area and in the diagonal band of Broca. These results are discussed in relation to the aging in different regions.

Aging↗
PubMed1991

Effects of neonatal bilateral eye enucleation on postnatal development of the monoamines in posterior thalamus of the rat.

Levels of dopamine (DA), noradrenaline (NA) and 5-hydroxytryptamine (serotonin, 5-HT) and their metabolites, and the activities of tyrosine hydroxylase (TH), tryptophan hydroxylase (TPH) and monoamine oxidase A and B (MAO-A and MAO-B) have been determined in the rat posterior thalamus after enucleation during postnatal development. DA and 5-HT turnover rate have been measured as 3,4-dihydroxyphenylalanine (DOPA) and 5-hydroxytryptophan (5-HTP) accumulation rates after central decarboxylase inhibition by 3-hydroxybenzylhydrazine (NSD-1015). The major changes were an increase in noradrenergic and serotoninergic metabolism in enucleated animals compared with control animals. A decrease of the MAO-A to MAO-B ratio during postnatal development was found.

5-Hydroxytryptophan↗
PubMed1991

Turnover of dopamine and serotonin and their metabolites in the striatum of aged rats.

Turnover of dopamine (DA), serotonin [5-hydroxytryptamine (5-HT)], and their metabolites has been measured in adult and aged rats. Turnover rates of 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), and 5-hydroxy-3-indoleacetic acid (5-HIAA) have been assayed from the disappearance rates after blocking by pargyline inhibition of monoamine oxidase (MAO) and from the accumulation rates by probenecid inhibition of the probenecid-sensitive transport system. DA and 5-HT turnover rates have been measured as accumulation rates of 3,4-dihydroxyphenylalanine and 5-hydroxytryptophan, respectively, after central decarboxylase inhibition by 3-hydroxybenzylhydrazine (NSD-1015) and as accumulation rates of DA and 5-HT after pargyline inhibition of MAO. The DA turnover rate after NSD-1015 was 23.9% lower in aged rats than in adults, whereas after pargyline there was no significant difference between the two age groups. The HVA fractional rate constant and turnover after pargyline were lower in aged rats than in adults, and HVA turnover after probenecid was higher in aged rats than in adults. The DOPAC-HVA pathway seems to be reinforced at the expense of DOPAC conjugation. In aged and adult rats whose 5-HT steady-state levels were not statistically different, the 5-HT turnover rate after pargyline and NSD-1015 treatment was lower in aged rats than in adults. An increase of 5-HIAA levels after pargyline and probenecid treatment in aged rats could be due to the handling stress.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1991

Effects of central epinephrine synthesis inhibition on stress-induced prolactin secretion in male rats.

1. The present study was designed to examine the role of central epinephrine pathways in the control of stress-induced prolactin secretion in male adult Wistar rats. 2. Intracerebroventricular administration of two epinephrine synthesis inhibitors, SKF 64139 (5 and 10 micrograms/rat) and LY 134046 (10 and 20 micrograms/rat), 6 h before the onset of immobilization stress blocked prolactin secretion in a dose-dependent manner. Prolactin values before stress were about 4.0 ng/ml and increased to almost 50 ng/ml in the control group. SKF 64139 injection in the higher dose (10 micrograms/rat) induced a complete blockade of the stress-induced prolactin release, whereas partial blockade was observed after the higher dose (20 micrograms/rat) of LY 134046. 3. Salbutamol pretreatment (10 micrograms/rat) completely restored stress-induced prolactin secretion in animals receiving a central injection of both epinephrine synthesis inhibitors under the same conditions as described above. 4. It is suggested that epinephrine pathways in the brain play an important role in the control of prolactin release occurring during immobilization stress.

Albuterol↗
PubMed1991

Pharmacologic characterization of GABAA/benzodiazepine receptor in rat hippocampus during aging.

We have characterized the pharmacologic properties of the gamma-aminobutyric acid (GABAA)/benzodiazepine receptor complex in hippocampal membranes from 3-month- and 24-month-old Wistar rats. No major changes were found in [3H]flunitrazepam or [3H]muscimol binding parameters. Neither the dissociation constant(s) nor the Bmax for either ligand seemed to be modified during aging in hippocampus. Furthermore, the allosteric interaction between the barbiturates binding site and the GABA binding site, determined by pentobarbital stimulation of [3H] muscimol binding, remained unaltered. However, there was a significant increase with aging in the efficacy of the GABA-enhancement of [3H]flunitrazepam binding. On the other hand, we have also detected a significant increase in the proportion of type I benzodiazepine receptor in 24-month-old hippocampal membranes. We propose that the age-related increase in the efficacy of GABA-enhancement of [3H]flunitrazepam binding could be correlated with the increase in the proportion of type I benzodiazepine receptor. Based on these results it is tempting to speculate that the age-dependent modifications on the GABAA/benzodiazepine receptor might reflect an age-dependent neuronal degeneration of the hippocampus or the hippocampal formation.

Aging↗