Biomedical subjects

J Cano

Publications and source records attributed to J Cano.

At least 127 records · Page 7Linked to original sources

PubMed1993

Are bilateral nigrostriatal dopaminergic pathways functionally linked in the rat brain? A microdialysis study in conscious rats.

In the present study, we have infused 6 prototypical drugs known to affect nigrostriatal dopaminergic neurons (kainate, baclofen, muscimol (10 mumol/l), picrotoxin (50 mumol/l), tetrodotoxin (TTX) (5 mumol/l) and 1-methyl-4-phenylpyridinium ion (MPP+) (10 mmol/l) via a microdialysis probe unilaterally into the left substantia nigra. During the infusion of these compounds, the extracellular content of dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC) was recorded simultaneously via microdialysis cannulas in both left and right striatum. Intranigral infusion of TTX, MPP+ and baclofen decreased dopamine release in the ipsilateral striatum, whereas muscimol, picrotoxin and kainate increased dopamine release. No changes were seen in the extracellular content of dopamine in the contralateral striatum. During all experiments, extracellular DOPAC increased in the ipsilateral striatum. No changes were seen in the extracellular content of DOPAC in the contralateral striatum. The present data provide no evidence that the bilateral nigrostriatal dopaminergic pathways are functionally linked in the rat brain.

1-Methyl-4-phenylpyridinium↗

PubMed1993

Regulation of prefrontal cortical dopamine release by dopamine receptor agonists and antagonists.

The effect of dopamine D1 and D2 receptors agonists and antagonists on extracellular dopamine release was evaluated by microdialysis in the prefrontal cortex. Nomifensine (5 microM) was included in the Ringer solution during the experiments. Cortical dopamine release was tetrodotoxin- and calcium-dependent and was stimulated by high potassium (60 mM) Ringer solution. 1-Methyl-4-phenylpyridinium ion (MPP+) (10 mM) increased the extracellular output of dopamine. SKF-38393 decreased the release of dopamine in a dose-related manner to about 80, 40 and 0% of the control values at 0.1, 1 and 10 microM, respectively. The decrease produced by SKF-38393 (10 microM) was partially antagonized by SCH-23390 at a concentration of 1 microM. Perfusion of CY-208243 (10 microM) produced a decrease in the release of dopamine to about 70% of controls. Quinpirole, at a concentration of 10 microM, produced a decrease in the release of dopamine to about 65% of controls. SCH-23390 and sulpiride, at 10 microM, increased the extracellular output of dopamine to about 150% of controls. These results indicate that dopamine D1 and D2 receptors are implicated in the autoregulation of dopamine release in the prefrontal cortex.

1-Methyl-4-phenylpyridinium↗

PubMed1993

Protective effect of deprenyl against 1-methyl-4-phenylpyridinium neurotoxicity in rat striatum.

Rats were treated with deprenyl for 3 weeks. Afterwards, slices of the corpus striatum were incubated with 1-methyl-4-phenylpyridinium ion (MPP+). Concentrations of dopamine and its metabolite concentrations were assayed. The effect of MPP+ in animals treated with deprenyl was smaller than in controls, indicating that deprenyl protects against MPP+. We also measured superoxide dismutase (SOD) and catalase activities and carbonyl group content of the proteins. Both activities increased in deprenyl-treated rats, and the amount of carbonyl groups was unchanged. These results suggest that the protective effect of deprenyl is independent of the monoamine oxidase-B inhibitor and of the induction of SOD and catalase activities.

1-Methyl-4-phenylpyridinium↗

PubMed1993

Turnover of monoamines in hippocampus of rats fed on vitamin E-deficient diet.

Turnover of noradrenaline (NA), dopamine (DA), serotonin (5-hydroxytryptamine; 5-HT) and their metabolites has been measured after a 15-day vitamin E-deficient diet in adult hippocampus. Moreover, we have measured in vitro receptor binding of [3H]5-HT in hippocampal membranes from control and vitamin E-deficient rats. Turnover rates of 3,4-dihydroxyphenylacetic acid (DOPAC) and 5-hydroxy-3-indolacetic acid (5-HIAA) have been assayed from the disappearance rates after blocking by pargyline inhibition of monoamine oxidase (MAO). DA, NA, 5-HT, normetanephrine (NMN) and 3-methoxytyramine (3-MT) turnover rates have been measured as accumulation rates of DA, NA, 5-HT, NMN and 3-MT after pargyline inhibition of MAO. An increase was found in the turnover rate of DA between control and experimental animals. In contrast, no changes were found in the turnover rate of 3-MT and DOPAC. No change was found in the turnover rate of NA although there was an increase of the turnover rate of NMN in vitamin E-deficient diets. No changes was found in the turnover rate of 5-HT although there was a decrease of 5-HIAA turnover rate in the animals fed on a low vitamin-E diet. With respect to the 5-HT1 receptors, no changes were found in the affinity (kd) but the receptor number (Bmax) was increased in vitamin E-deficient rats.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1993

Effects of age and dopamine agonists and antagonists on striatal dopamine release in the rat: an in vivo microdialysis study.

The in vivo microdialysis technique was used to measure the extracellular output of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) in adult and aged rats; as well as in response to the perfusion of dopamine agonists and antagonists, high-potassium Ringer solution and 1-methyl-4-phenyl-pyridinium ion (MPP+). The DA basal release before the drug treatment was higher in adult rats compared with the aged animals. The perfusion of dopaminergic drugs (nomifensine, sulpiride and quinpirole) through the probe at 1 microM concentration produced the same effect on DA, DOPAC and HVA outflow in adult and aged rats. 5-HIAA levels were not affected. The application of a high-potassium (60 mM) Ringer solution did not produce any significant difference on DA, DOPAC, HVA and 5-HIAA extracellular content when adult and aged rats were compared. The perfusion of MPP+ (1 mM) for 15 min produced a greater increase in DA release in aged than in adult rats. Greater susceptibility in the adult rats could explain these results.

1-Methyl-4-phenylpyridinium↗

PubMed1993

Influence of polyhydroxylic cosolvents on papain thermostability.

Papain thermostability was studied, and non-first-order deactivation kinetics were observed. The results obtained were analyzed by a two-step series-type deactivation model involving the native and active enzyme, an active intermediate enzyme state, and a final inactive state, with excellent agreement. The influence of different polyhydroxylic cosolvents (ethylene glycol, glycerol, erythritol, xylitol and sorbitol) on the thermostability of papain at 60 degrees C was also studied. Analysis of the results by the assayed model showed that the main protective effect of cosolvents was observed in the second step of the deactivation profile. The results obtained were analyzed as a function of both the thermodynamic parameters and a protective effect, defined as the ratio of papain half-lives (with and without cosolvents) for the second deactivation step, showing in both cases an important stabilizing effect of these cosolvents on the enzyme. The overall protective effect of cosolvents was also related simultaneously to their concentration and their water activity-depressing power.

Biotechnology↗

PubMed1993

Ageing and monoamine turnover in the lateral geniculate nucleus and visual cortex of the rat.

The effects of ageing on the turnover of dopamine, noradrenaline and serotonin in the lateral geniculate nucleus and the visual cortex were evaluated, using high performance liquid chromatography (HPLC) with electrochemical detection. Compared to adult animals, aged rats showed more changes in the visual cortex than in the lateral geniculate nucleus, with dopamine turnover decreased in both structures and noradrenaline turnover unaltered. Changes in serotonin turnover were witnessed only in the visual cortex. A decrease in the monoamine oxidase-A to -B ratio was also observed with increased age for both the lateral geniculate nucleus and visual cortex.

Aging↗

PubMed1993

Effects of a short period of vitamin E-deficient diet in the turnover of different neurotransmitters in substantia nigra and striatum of the rat.

Measurement of turnover of dopamine, noradrenaline and serotonin and their metabolites was assessed in striatum and substantia nigra of adult female rats that were fed control or vitamin E-deficient diets over 15 days. The levels and turnover of dopamine increased and the levels of serotonin decreased in both structures whereas serotonin turnover decreased only in striatum. No change was found in the turnover rate of noradrenaline between control and experimental animals. However, the most striking result was the increase of dopamine turnover found in substantia nigra. This dopamine increase was accompanied by an increase in 3-methoxytyramine turnover which seems to indicate an increase in dopamine release after vitamin E deficiency. The present study indicates that the nigrostriatal dopamine neurons are susceptible to the deficiency of vitamin E. Moreover, these data suggest that substantia nigra may be more susceptible to damage from vitamin E deficiency than striatum.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1993

Changes in neurotransmitters in superior colliculus after neonatal enucleation: biochemical and immunocytochemical studies.

The turnover rate of dopamine and serotonin and the level of glutamate in superior colliculus are increased in adult, neonatally enucleated rats compared with normal control adult animals. Moreover, immunocytochemical data showed that the stratum zonale and the stratum griseum superficiale of the superior colliculus, specifically of bienucleated rats, display a dense network of serotonin-immunoreactive fibres, suggesting an increase in serotoninergic innervation. At the electron microscope level, serotonin-immunoreactive fibres and large postsynaptic serotonin-immunoreactive profiles exhibiting microtubules could be observed in the stratum zonale and the stratum griseum superficiale of the bienucleated rat. These results suggest that neonatal enucleation produces reorganization of serotoninergic and glutamatergic inputs. It is possible that serotonin may exert a profound influence upon collicular function.

5-Hydroxytryptophan↗

PubMed1993

Low selenium diet affects monoamine turnover differentially in substantia nigra and striatum.

Turnover of dopamine, noradrenaline, serotonin, and their metabolites has been measured in striatum and substantia nigra of adult female rats that were fed control or selenium-deficient diets for 15 days. In addition, the glutathione peroxidase activity has been studied. The most striking result was the increase of dopamine turnover (63%) and 3-methoxytyramine turnover (55%) in substantia nigra between control and experimental animals. On the other hand, no changes were found in the turnover rate of dopamine and its metabolites in the striatum. Likewise, no changes were found in noradrenaline turnover in substantia nigra. In the striatum, there was a significant increase of serotonin turnover versus no change for 5-hydroxy-3-indoleacetic acid. However, in the substantia nigra, serotonin turnover did not show significant changes, whereas 5-hydroxy-3-indoleacetic acid turnover decreased. At the same time, glutathione peroxidase activity significantly decreased in both structures after selenium-deficient diets. These results suggest that a selenium-deficient diet for a short period of time decreases brain protection, principally in the substantia nigra, against oxidative damage.

Animals↗

PubMed1993

In vivo release of dopamine from rat striatum, substantia nigra and prefrontal cortex: differential modulation by baclofen.

1. The effect of baclofen, a GABAB receptor agonist, on the release of dopamine from the striatum (ST), substantia nigra (SN) and prefrontal cortex (PFC) of the rat was examined by intracerebral microdialysis. 2. Perfusion of baclofen 50 microM did not affect the striatal release of dopamine. However, dopamine release was markedly reduced in the SN and PFC. 3. 3,4-Dihydroxyphenylacetic acid and homovanillic acid output increased in the ST and decreased in the SN and PFC when baclofen was perfused through the microdialysis probe. 5-Hydroxyindoleacetic acid levels were not affected in any experimental condition by baclofen perfusion. 4. The results suggest that GABAB receptors modulate the release of dopamine in the SN and PFC, but do not affect the striatal release of dopamine, which indicates that the role of GABA receptor activation is different in the dopaminergic terminals of the ST and PFC.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1993

Glycylglycylphenylalaninamide synthesis catalysed by papain in a medium containing polyols.

The influence of several polyols (ethylene glycol, glycerol, erythritol, xylitol and sorbitol) on both the thermostability and tripeptide(Gly-Gly-PheNH2)-synthesis capability of papain was studied at 60 degrees C. The results obtained from the thermostability studies on papain showed that polyols increased the half-life time of the esterase activity of the enzyme proportionally to their molecular size and concentration, except for ethylene glycol. The presence of polyols, as water-activity-depressing agents, also enhanced the enzyme activity for Gly-Gly-PheNH2 synthesis in a way which was directly proportional to the molecular size of the polyol molecule and its water-activity-depressing power. A linear relationship between the increase in the synthetic/hydrolytic activity ratio and the overall concentration of hydroxy groups in the reaction media was obtained, indicating that these latter groups are mainly responsible for the modification of the catalytic behaviour of the enzyme, as a result of a change in their microenvironment.

Amino Acid Sequence↗

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↗