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J Aceves

Publications and source records attributed to J Aceves.

At least 37 records · Page 2Linked to original sources
PubMed1996

Noradrenaline-induced inositol phosphate formation in rat striatum is mediated by alpha 1A-adrenoceptors.

The aim of this study was to assess the contribution of alpha 1-adrenoceptor subtypes to noradrenaline (NA)-induced inositol phosphate formation in rat striatum. In cross-chopped slices and in the presence of 10 mM LiCl, NA stimulated the accumulation of [3H]inositol phosphates. After 60-min incubation with 100 microM NA, [3H]IP1 was the major product detected (82 +/- 3% of total [3H]inositol phosphates). Best-fit values for the concentration-response curve for NA-induced [3H]IP1 accumulation yielded an EC50 of 9.4 +/- 1.1 microM, maximum effect of 210 +/- 3% of basal, and Hill coefficient (nH) of 1.1 +/- 0.1. Pre-treatment of the slices for 30 min with the alkylating agent chloroethylclonidine (100 microM) failed to decrease significantly the response to 100 microM NA. Inhibition curves for four alpha 1-antagonists, (+)-niguldipine, prazosin, WB-4101 and 5-methylurapidil (5-MU), best-fit to a single-site model with pKi values of 9.4 ((+)-niguldipine), 9.2 (prazosin and WB-4101) and 8.8 (5-MU). The putative alpha 1 D-selective antagonist BMY 7378 reduced the response to NA only partially (30 +/- 3% inhibition at 1 microM: pKi 7.24). NA-induced [3H]IP1 accumulation was significantly reduced (to 20 +/- 9% of controls) by Ca2+ removal and increased as the extracellular Ca2+ concentration was raised from nominally zero (no added Ca2+) to 1 mM Ca2+. NA-induced [3H]IP1 accumulation was reduced by both the non-selective Ca2+ channel blocker Ni2+ (58 +/- 3% inhibition at 2 mM) and nimodipine, an antagonist of L-type voltage-operated Ca2+ channels (77 +/- 4% inhibition at 3 microM). Taken together these results indicate that NA-induced inositol phosphate formation in striatal slices is mediated by activation of alpha 1A-adrenoceptors coupled to Ca2+ entry and Ca2+ activation of phospholipase C.

Adrenergic alpha-1 Receptor Agonists↗
PubMed1996

Research in pediatric residency programs.

BACKGROUND AND OBJECTIVES: We have required residents in pediatrics at the Cleveland Clinic Foundation to give research presentations since 1989; this article reviews our experience with this program. Additionally, we sought to determine how many other accredited pediatric programs in the United States also require this. METHODS: Retrospective review of the Cleveland Clinic program; descriptive statistics of other United States residency programs, obtained by questionnaire. RESULTS: Pediatric residents at the Cleveland Clinic have given 108 research presentations since 1989, and have developed 33 (30.5%) of them into manuscripts or abstracts. We mailed questionnaires to 215 pediatric residency program directors and received responses from 177 (82%). Of these, 48 (27%) indicated their programs had a research requirement; residents could present their findings in departmental meetings or submit an abstract or manuscript to a professional society or journal. Respondents cited several barriers to research: residents are too busy, there are too few faculty members to mentor them, financial resources are limited, and there is no residency review committee requirement. CONCLUSIONS: Even though only approximately one fourth of the pediatric residency programs in the United States require research, we feel it is worthwhile experience. Despite barriers, residents can and do perform research and publish their findings.

Curriculum↗
PubMed1995

5-Hydroxytryptamine increases spontaneous activity of subthalamic neurons in the rat.

The effect of 5-hydroxytryptamine on the spontaneous activity of neurons of the subthalamic nucleus was examined by recording the extracellular unitary activity in an in vitro slice preparation. The most frequent response to 5-hydroxytryptamine (84% of 57 neurons tested) was an increase (twofold of basal at 10 microM) of the discharge frequency. The EC50 for the 5-hydroxytryptamine-induced effect was 1.8 +/- 0.5 microM (mean +/- SEM). The response was dose-dependently blocked by the serotoninergic antagonist mianserin and was not prevented by removal of calcium ions from the perfusing buffer. These results indicate that the serotoninergic input to the rat subthalamic nucleus exerts a postsynaptic excitatory action on most neurons of the nucleus.

Animals↗
PubMed1995

D-1 receptor mediated modulation of the release of gamma-aminobutyric acid by endogenous dopamine in the basal ganglia of the rat.

1. Presynaptic D1 receptors are present on GABAergic terminals of neostriatal projections. 2. By activating these receptors, exogenous dopamine enhances the release of GABA. 3. Here the authors have explored whether endogenous dopamine was also able to activate the receptors, thus enhancing GABA release. 4. The effect of methamphetamine, a dopamine releaser, on the release of tritiated GABA was studied in slices of substantia nigra pars reticulata, entopeduncular nucleus and caudate-putamen, targets of the striatal projections. 5. Methamphetamine enhanced the release of the label. However the enhancement required an intact dopaminergic innervation, since it was lost in slices isolated from rats with 6-hydroxydopamine-induced lesions of the dopaminergic nigrostriatal system. 6. The activation of the receptors by endogenous dopamine was also judged by the effect of the selective D1 antagonist SCH 23390 in potassium depolarized slices. By preventing activation of the receptors by dopamine released as result of depolarization, the antagonist reduced GABA release. In 6-OHDA lesioned slices, no reduction was observed, even though the slices were also depolarized. 7. The results indicate that endogenous dopamine enhances GABA release from striatal terminals in the pars reticulata of the substantia nigra, entopeduncular nucleus and caudate-putamen. This would facilitate GABAergic neurotransmission. 8. The study suggests that the function of DA in the basal ganglia is widespread, modulating not only the firing of the striatal efferent neurons but also the transmission of the fired impulses across synapses in the target nuclei of these neurons.

Animals↗
PubMed1994

Activation of subthalamic neurons produces NMDA receptor-mediated dendritic dopamine release in substantia nigra pars reticulata: a microdialysis study in the rat.

Here we have studied whether the activation of the subthalamic neurons induces the release of dopamine (DA) from dopaminergic dendrites in the pars reticulata of the substantia nigra. Subthalamic neurons were activated by carbachol microinjected into the subthalamic nucleus. A microdialysis probe was implanted in the medial aspect of the pars reticulata to collect samples of the perfusate. Carbachol (1 microgram/0.25 microliter saline) enhanced (58 +/- 8% over basal values) nigral DA release. The enhancement was fully blocked by the NMDA antagonist AP5 added to the microdialysis medium perfusing the pars reticulata. Perfusion of the pars reticulata with NMDA also increased (125 +/- 25% over basal) nigral DA release. Again, AP5 reversed the effect. These results suggest that activation of the glutamatergic subthalamonigral pathway enhances dendritic DA release by activating NMDA receptors present on dopaminergic dendrites.

Animals↗
PubMed1994

Cholinergic stimulation of rostral and caudal substantia nigra pars compacta produces opposite effects on circling behavior and striatal dopamine release measured by brain microdialysis.

Turning in circles is among the behaviors elicited by unilateral cholinergic stimulation of the substantia nigra. Recent studies have shown that microinjection of cholinergic agonists into the substantia nigra pars compacta increases dopamine release and turnover in the striatum of anesthetized rats [Hernández-López et al. (1992) Brain. Res. 598, 114-120; Blaha and Winn (1993) J. Neurosci, 13, 1035-1044]. In this study, the relationship between circling behavior and striatal dopamine release following cholinergic stimulation of the substantia nigra pars compacta neurons was assessed by brain microdialysis in awake rats. The results indicate that cholinergic stimulation of the substantia nigra pars compacta with the mixed nicotinic-muscarinic cholinergic agonist carbachol modulates striatal dopamine release, and this effect is accompanied by circling behavior and stereotypies. Microinjection of carbachol (109 nmol) in the caudal portions of the substantia nigra pars compacta induced contralateral circling associated with an increase of dopamine release in neostriatum. On the contrary, ipsilateral circling and reduction of striatal dopamine release was elicited when the same dose of the drug was applied in the rostral portions of the substantia nigra pars compacta. The above findings are in accordance with recent electrophysiological studies suggesting the existence of sub-populations of nigrostriatal dopaminergic neurons, and indicate that the substantia nigra pars compacta is functionally compartmentalized. We conclude that the cholinergic input to the substantia nigra pars compacta could modulate the motor behavior through regulating the firing rate of nigrostriatal dopaminergic neurons and dopamine release in the neostriatum.

Animals↗
PubMed1994

Neurotransmitter levels in cerebrospinal fluid in relation to severity of symptoms and response to medical therapy in Parkinson's disease.

Determinations of biopterin (BP), homovanilic acid (HVA), glutamic acid (GTA), and glutamine (GT) levels in cerebrospinal fluid (CSF) obtained through a lumbar tap were performed in 20 parkinsonian patients in different stages of evolution and without medication. In patients with motor symptoms not related to Parkinson's disease (dystonia, dyskinesia and essential tremor) (n = 4). In 7 other neurological patients subjected to spinal tap for diagnostic procedures neurotransmitters were also determined and taken as control groups. In 14 of the patients with Parkinson's disease, the symptoms were evaluated using conventional scales (UPDS, NYPDS, NWPDS, Schwab and England, and Hoehn and Yahr scale). The amplitude and the frequency of tremor were quantitatively evaluated through a single plane accelerometer Grass SP-1, akinesia was measured through reaction time to auditory stimuli, and rigidity through the speed of lineal movement. Evaluations were performed with the patient not on any medication for 1 week and repeated 1 h after the intake of 250 mg of 200/50 L-dopa/carbidopa preparation (Sinemet) and on a different day after the intake of biperiden (Akineton) 6 mg/day. Differences in neurotransmitter or metabolites levels between Parkinson's disease and control groups were determined through an independent Student's t test. Correlation between severity of symptoms in the scales and for each individual symptom measured through the quantitative tests and the levels of neurotransmitters in CSF were evaluated through the Pearson correlation analysis test. Modifications in the motor performance after administration of Sinemet and Akineton, and the levels of neurotransmitters were indirectly determined. RESULTS. (1) There were significant differences between the levels of BP and GT in patients with Parkinson's disease and control groups, (2) lower GTA levels correlated with more severe rigidity and akinesia, and with the best response to the administration of L-dopa and may be an important marker for prognosis, and (3) lower levels of GT correlated with least akinesia, but not with tremor, which may indicate that the akinesia depends on other biochemical abnormalities besides dopamine depletion.

Adult↗
PubMed1993

Appearance of EMG activity and motor asymmetry after unilateral lesions of the dopaminergic innervation to the subthalamic nucleus in the rat.

The effects of unilateral injections of 6-hydroxydopamine into the subthalamic nucleus on muscular rigidity and on motor behavior were examined. Muscular rigidity was judged by the appearance of electromyographical activity in the gastrocnemius-soleus muscle and motor behavior by the turning induced by DL-methamphetamine. The unilateral injection of 6-hydroxydopamine produced the appearance of electromyographical activity ipsilateral to the injected side and ipsilateral turning in response to systemic administration of DL-methamphetamine. These results suggest that the dopaminergic innervation exerts a tonic inhibitory action on the spontaneous activity of the subthalamic neurons. The loss of this action would cause muscular rigidity and motor asymmetry.

Animals↗
PubMed1993

Carbachol-induced phosphoinositide metabolism in slices of rat substantia nigra pars reticulata.

Carbachol produced an approximately 2-fold stimulation, with respect to basal, of [3H]inositol monophosphate ([3H]IP1) accumulation in microdissected slices of rat substantia nigra pars reticulata (SNr), measured as a percentage of [3H]inositol incorporation. The response to carbachol was inhibited by 75 +/- 7% by 1 microM pirenzepine, consistent with a muscarinic M1 receptor-mediated response. Carbachol-induced [3H]IP1 accumulation was not reduced by pretreatment of the SNr slices with NMDA, in contrast to the 85% inhibition observed in striatal slices. The results suggest that measurement of carbachol-induced phosphoinositide hydrolysis may be a feasible approach for studying muscarinic M1 receptor function in slices of SNr.

Animals↗
PubMed1992

A cholinergic input to the substantia nigra pars compacta increases striatal dopamine metabolism measured by in vivo voltammetry.

3,4-Dihydroxyphenylacetic acid (DOPAC) and ascorbic acid (AA) were measured by differential pulse voltammetry in the neostriatum of anesthetized rats. Physostigmine (2.3 nmol) applied into the substantia nigra pars compacta (SNc), increased DOPAC concentration in the ipsilateral neostriatum, but did not modify AA levels. The largest increase of striatal DOPAC (37 +/- 8% above basal) was observed when physostigmine was applied at less than 0.5 mm from SNc, and decreased with increasing distance of the injection site from the pars compacta region. Chemical stimulation of the pedunculopontine tegmental nucleus (PPN) with kainic acid (2.3 nmol) increased both DOPAC and AA concentration in the ipsilateral neostriatum. Pretreatment with the muscarinic antagonist scopolamine (5 mg/kg, i.p.) inhibited the increase of striatal DOPAC from 20 to 70 min after kainic acid injection into the PPN, whereas the increase of AA was reduced from 90 to 160 min. By contrast, the nicotinic antagonist mecamylamine (4 mg/kg, i.p.) did not inhibit neither DOPAC nor AA increase elicited by the chemical stimulation of PPN. These results support the existence of cholinergic neurotransmission within the SNc that increases the firing rate of nigrostriatal dopaminergic neurons, enhancing dopamine turnover in neostriatum without changes in AA release. They also suggest that the PPN could be the origin of cholinergic afferents to the SNc that modulate the activity of dopaminergic neurons, through activation of muscarinic cholinergic receptors. Finally, the activation of a multisynaptic loop involving a cholinergic pathway which modulates the activity of the glutamatergic corticostriatal neurons is postulated to explain the increase of AA in neostriatum observed after PPN stimulation.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1992

NMDA receptor mediates dopamine release in the striatum of unanesthetized rats as measured by brain microdialysis.

We have studied the characteristics associated with the activation of the N-methyl-D-aspartate (NMDA) subtype of the glutamate receptor on the release of dopamine (DA) in the striatum of awake rats as measured by brain microdialysis technique. NMDA dose-dependently stimulated the striatal DA release in Mg(2+)-free Ringer's solution. The stimulation was significant at 90 microM and the maximum observed effect was at the highest concentration tested (800 microM). The selective NMDA receptor antagonist, 2-amino-5-phosphonovalerate (AP5; 300 microM), blocked the stimulatory effect of NMDA. The NMDA-induced release of DA was reduced by 1.2 mM Mg2+ and totally blocked by 2.5 mM of the cation. Glycine (200 microM) potentiated the response evoked by 300 microM NMDA while 7-chloro-kynurenate (100 microM), an antagonist of the glycine site, reduced markedly this response. Neither atropine (100 microM) nor tetrodotoxin (TTX) (5 microM) prevented the stimulatory effect of NMDA. These results suggest that glutamate released from corticostriatal terminals presynaptically stimulates the release of DA via an NMDA receptor.

2-Amino-5-phosphonovalerate↗
PubMed1992

Activation of D1 receptors stimulates accumulation of gamma-aminobutyric acid in slices of the pars reticulata of 6-hydroxydopamine-lesioned rats.

D1 dopamine receptors are present on terminals of striatal neurons to the pars reticulata of the substantia nigra in the rat. Here we have studied the effect of the activation of these receptors on the synthesis of gamma-aminobutyric acid (GABA) in slices of the pars reticulata of the substantia nigra isolated from 6-hydroxydopamine-lesioned rats. The synthesis was judged by the accumulation of GABA after inhibiting GABA transaminase with aminooxyacetic acid. Both dopamine and SCH 23390, a D1 agonist, stimulated the synthesis. The effect of both compounds was blocked by SCH 23390, a D1 antagonist, but not by sulpiride, a D2 antagonist. In the absence of receptor activation, the synthesis was very slow. The results suggest a trophic influence of dopamine upon the synthesis of GABA via D1 receptors.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1992

GABAB receptor activation partially inhibits N-methyl-D-aspartate-mediated tyrosine hydroxylase stimulation in rat striatal slices.

The effect of the GABAB agonist, (+/-)-baclofen, on the N-methyl-D-aspartate (NMDA)-mediated stimulation of tyrosine hydroxylase activity was investigated in slices of rat striatum. Tyrosine hydroxylase activity was stimulated by NMDA in a concentration-dependent manner (EC50, 1.3 +/- 0.3 microM; maximum stimulation 194 +/- 7% of basal activity). The action of NMDA was reversed by the NMDA antagonist, 2-amino-5-phosphonovalerate (AP-5). (+/-)-Baclofen (100 microM) decreased the maximum effect of NMDA by 24 +/- 2% without significantly modifying its EC50. The IC50 for the inhibitory action of (+/-)-baclofen was 4.2 +/- 1.2 microM. These results show that GABAB receptor activation modulates NMDA-stimulated tyrosine hydroxylase activity, further supporting the possibility of a role of GABA in the regulation of striatal dopaminergic neurotransmission.

Animals↗
PubMed1992

Glutamate stimulation of tyrosine hydroxylase is mediated by NMDA receptors in the rat striatum.

We have studied the action of glutamate on striatal tyrosine hydroxylase activity and determined which type of glutamate receptors are involved. Glutamate stimulated (EC50 = 4 +/- 2 microM) the activity of tyrosine hydroxylase in slices of rat neostriatum. The selective N-methyl-D-aspartate (NMDA) receptor antagonist 2-amino-5-phosphonovalerate (10 microM) blocked the stimulation; however, both the non-NMDA receptor antagonist glutamate diethyl ester (10 microM) and the general excitatory amino acid antagonist kynurenate (10 microM) had no effect. NMDA was even more potent than glutamate in stimulating tyrosine hydroxylase activity. Quisqualate (100 microM) only slightly stimulated the enzyme, and kainate had practically no effect. Omission of Mg2+ from the incubation medium potentiated the glutamate stimulation. Neither tetrodotoxin nor atropine prevented the stimulation. These results suggest that glutamate stimulates striatal tyrosine hydroxylase activity via NMDA receptors. The lack of effect of tetrodotoxin and atropine suggests that glutamate acts on NMDA receptors located on the dopaminergic nigrostriatal terminal. The stimulation may involve the entry of Ca2+ into the terminal through the NMDA receptor ionophore, since a Ca(2+)-free medium or cadmium totally blocked the stimulation of the enzyme by glutamate.

2-Amino-5-phosphonovalerate↗
PubMed1992

Charybdotoxin and apamin sensitivity of the calcium-dependent repolarization and the afterhyperpolarization in neostriatal neurons.

1. Intracellular recordings from neostriatal neurons in an in vitro slice preparation of the rat brain were used to analyze the pharmacological sensitivity of the action potential (AP) repolarization and the afterhyperpolarization (AHP) that follows a single action potential. The interspike voltage trajectory and the AHP could be divided into two main parts: a fast component lasting a few milliseconds and better observed during a train of spikes, and a slow component lasting approximately 250 ms and that comprises the main portion of the AHP. In some cells, a slow (up to 1 s) component of low amplitude was also detected. 2. Single APs were elicited at two imposed membrane potentials (around -60 and around -80 mV). The AP amplitude was larger, the repolarization rate was faster, and the duration was shorter when spikes were evoked at -80 mV. When measured from the -60 mV holding potential, the afterpotential was an AHP with peak amplitude of -5 mV. The afterpotential became a delayed depolarization (DD) at -80 mV. 3. Firing frequency adaptation was voltage sensitive. The firing of APs induced by long intracellular current pulses from a holding potential of -80 mV exhibited only a slow-frequency adaptation (time constant of seconds). However, at -60 mV, an initial and faster frequency adaptation was evident (time constant of tens of milliseconds). 4. The Ca2+ channel blocker Cd2+ retarded AP repolarization rate. This effect correlated with a significant block of the fast and slow components of the AHP. In contrast, Ni2+ had no significant effects on the same parameters.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗
PubMed1992

[Vertebral hemangioblastoma: an atypical localization].

The case of a 53 year old patient with spastic paraparesis, sphincter function impairment and a deficit of sensation at the T 10 level of 2 months of evolution is presented complementary explorations (simple x-ray of the vertebrae, CT, MR and arteriography) demonstrated the presence of a vascular lesion affecting the 7th thoracic vertebra and which invaded the rachidian channel, compressing the spinal cord. Biopsy study of the intraspinal lesion was diagnosed as hemangioblastoma. A spinal hemangioblastoma with involvement of the vertebra at the same level is reported. The authors present three diagnostic hypothesis: the lesion is a vertebral hemangioblastoma with invasion of the rachidian channel with a evolution similar to vertebral angioma; the lesion is a vertebral angioma which invaded the channel differentiated into hemangioblastoma in its intraspinal position; or it is a spinal hemangioblastoma which has infiltrated the vertebra.

Epidural Neoplasms↗
PubMed1991

Activation of nigral M1 and M2 muscarinic receptors produces opposing effects on striatal 3,4-dihydroxyphenylacetic acid measured by in vivo voltammetry.

3,4-dihydroxyphenylacetic acid (DOPAC) was measured by differential pulse voltammetry in the neostriatum of anesthetized rats. DL-Muscarine (2.9 nmol) applied into the substantia nigra pars compacta, increased DOPAC concentration in the ipsilateral neostriatum. This effect was blocked by pirenzepine (2.8 nmol), and potentiated by AF-DX 116 (2.8 nmol). These results indicate the existence of two types of muscarinic receptors on dopaminergic neurons, whose activation produces opposing effects on dopamine metabolism in neostriatum.

3,4-Dihydroxyphenylacetic Acid↗