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E Fedele

Publications and source records attributed to E Fedele.

47 records · Page 3Linked to original sources
PubMed1990

Glycine enhances [3H]noradrenaline release from slices of rat hippocampus.

The effects of glycine on the release of [3H]noradrenaline ([3H]NA) have been investigated using rat hippocampus slices previously labeled with the radioactive catecholamine. Glycine (30-1000 microM) produced a potent and concentration-dependent increase of the release of [3H]NA evoked by 12 mM KCl. The effect of 1000 microM glycine was totally antagonized by 3 microM strychnine suggesting that, in rat hippocampus, glycine may regulate the release of NA by activating a receptor of the strychnine-sensitive subtype.

Animals↗
PubMed1990

Glycine stimulates [3H]noradrenaline release by activating a strychnine-sensitive receptor present in rat hippocampus.

Rat hippocampus slices were prelabeled with [3H]noradrenaline ([3H]NA) and depolarized by superfusion with KCl. The release evoked by 12 mM K+ was totally calcium-dependent and more than 90% tetrodotoxin (TTX)-sensitive. Glycine (0.1-1 mM) increased the K(+)-evoked [3H]NA overflow in a concentration-dependent manner. The effect of 1 mM glycine reached 300%. Strychnine (0.3 microM) shifted to the right the concentration-response curve for glycine. The effect of glycine (0.1 or 1 mM) was totally abolished by 3 microM strychnine but was unaffected by the GABAA receptor antagonist, bicuculline (10 microM), or by 100 microM of 1-hydroxy-3-aminopyrrolidone-2 (HA-966), a proposed antagonist of glycine at the strychnine-insensitive site located on the N-methyl-D-aspartate (NMDA) receptor. The effect of glycine was mimicked by L-serine, although less potently; the release of [3H]NA was enhanced by 200% in presence of 3 mM L-serine. At this concentration D-serine was ineffective. Strychnine shifted to the right the concentration-response curve for L-serine. Glycine (1 mM) had only a minor effect (less than 20% potentiation) on the release of [3H]NA evoked by 12 mM KCl in hippocampal synaptosomes. While the effect of glycine in slices was increased by decreasing the depolarizing concentration of K+ (about 500% potentiation at 9 mM K+), the response of synaptosomes remained minimal, even in presence of 9 mM KCl. Hippocampal synaptosomes prelabeled with [3H]glycine released the radiolabeled amino acid when exposed to superfusion with 12 mM KCl. The release of [3H]glycine was more than 75% calcium-dependent. The results suggest that the release of NA in rat hippocampus may be enhanced by glycine through the activation of a strychnine-sensitive receptor. This receptor does not seem to be located on noradrenergic terminals.

Animals↗
PubMed1989

Acetylcholine release from rat hippocampal slices is modulated by 5-hydroxytryptamine.

Experiments were performed with slices of rat hippocampus in order to investigate whether the release of acetylcholine in this area is modulated through 5-hydroxytryptamine (5-HT) receptors. The slices were prelabeled with [3H]choline then stimulated electrically twice for 4 min each at a frequency of 3 Hz. The overflow of tritium evoked was inhibited by exogenous 5-HT in a concentration-dependent manner. The 5-HT2 receptor agonist, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane HC1 ((+/-)-DOI), did not mimic 5-HT. The effect of 5-HT was antagonized by methiothepin but not by the 5-HT2 antagonist, ketanserin. The 5-HT1 agonist, 5-methoxy-3-[1,2,3,6-tetrahydropyridin-4-yl]-1H-indole (RU 24969), inhibited the electrically evoked overflow of tritium, whereas the 5-HT1A-selective agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), was ineffective. Methiothepin itself, but not ketanserin, increased the evoked overflow of tritium. In contrast, the overflow was inhibited by the 5-HT uptake blocker, 6-nitroquipazine. The evoked overflow was also reduced by d-fenfluramine, a serotonin releaser. The concentration-inhibition curve for d-fenfluramine was shifted to the right by methiothepin. It is concluded that the release of ACh in rat hippocampus may be tonically inhibited by 5-HT through the activation of receptors, possibly belonging to the 5-HT1B subtype.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1989

Functional damage of dopamine nerve terminals following intrastriatal kainic acid injection.

The release of [3H]dopamine ([3H]DA) previously taken up into rat striatal slices was studied one week after a monolateral intrastriatal injection of kainic acid (KA). Different releasing stimuli (electrical pulses, veratrine, high-K+) were applied. The electrically evoked release in the KA-lesioned striata was drastically reduced with respect to the unlesioned contralateral striata. In contrast, KA had no effect on the release of [3H]DA evoked by veratrine or high-K+. In unlesioned striatal slices, depolarized with 15 mM KCl, apomorphine reduced and (-)sulpiride increased the release of [3H]DA. The effect of apomorphine was antagonized by (-)sulpiride indicating the presence of an autoreceptor system similar to that seen in unlesioned striata stimulated electrically. However, the effects of apomorphine and of (-)sulpiride were dramatically reduced in K+-depolarized slices prepared from KA-lesioned striata. The results suggest that the axon terminals in KA-treated areas remain intact in several of their properties but may be damaged in some critical processes.

Animals↗
PubMed1989

Presynaptic mechanisms underlying the gamma-aminobutyric acid-evoked receptor-independent release of [3H]norepinephrine in rat hippocampus.

The effects of gamma-aminobutyric acid (GABA) on the spontaneous efflux of [3H]norepinephrine ([3H]NE) were studied in synaptosomes prepared from rat hippocampus and prelabelled with [3H]NE. It had been observed previously that, when synaptosomes were exposed in superfusion to GABA, the basal release of the tritiated catecholamine was enhanced, apparently with no involvement of the known GABA receptors. The mechanisms underlying this effect have now been investigated. The potency of GABA as a releaser of [3H]NE was decreased by lowering the Na+ content of the superfusion medium, and its effect disappeared at 23 mM Na+. The GABA-induced [3H]NE release was counteracted by the GABA uptake inhibitor N-(4,4-diphenyl-3-butenyl)nipecotic acid (SKF 89976A), but it was unaffected by the NE uptake blockers desmethylimipramine and nisoxetine. The GABA-induced release of [3H]NE was Ca2+-dependent and tetrodotoxin-sensitive. The data support the hypothesis that GABA provoked [3H]NE release by a novel mechanism which involves penetration into the noradrenergic nerve terminals through a GABA carrier located on the NE terminals themselves. This uptake process might be electrogenic and provoke depolarization of the nerve terminals, causing an exocytotic release of [3H]NE.

Animals↗
PubMed1989

Release of gamma-[3H]aminobutyric acid (GABA) from electrically stimulated rat cortical slices and its modulation by GABAB autoreceptors.

Slices of rat temporo-parietal cortex were prelabeled with gamma-[3H]aminobutyric acid ([3H]GABA), in the presence of the glial GABA uptake inhibitor beta-alanine. The slices were then superfused with a medium containing the GABA transaminase inhibitor aminooxyacetic acid and stimulated electrically (5 min, 2 msec, 36 mA at 5 or 10 Hz), in the presence of the neuronal GABA reuptake inhibitor SK&F 89976A [N-(4,4-diphenyl-3-butenyl)-nipecotic acid] and of beta-alanine. Representative experiments showed that the tritium released could be accounted for almost entirely by authentic [3H]GABA. The electrically evoked overflow of [3H]GABA was tetrodotoxin sensitive and largely calcium-dependent. Exogenous GABA, added to the superfusion medium at 3 to 30 microM, reduced in a concentration-dependent manner the electrically evoked (5 Hz) release of [3H]GABA. The GABAB receptor agonist (-)-baclofen, but not the GABAA receptor agonist muscimol, mimicked GABA and produced a concentration-inhibition curve almost superimposable to that of the natural transmitter. The effects of GABA and of (-)-baclofen were much more pronounced at 5 than at 10 Hz. The GABA-induced inhibition of [3H]GABA release was sensitive to the novel GABAB receptor antagonist beta-(p-chlorophenyl)-3-amino propyl phosphonic acid which, by itself, increased the [3H]GABA overflow. The inhibitory effect of GABA was not counteracted by the GABAA receptor antagonists bicuculline or SR 95531 [2-(3'-carbethoxy-2'-propenyl)-3-amino-6-paramethoxy-phenyl-pyr idazinium bromide]. The results are compatible with the presence in the rat cerebral cortex of autoreceptors mediating inhibition of GABA release and belonging to the GABAB type. These autoreceptors may be activated tonically under physiological conditions.

Animals↗
PubMedDate not supplied

Clinical and electrophysiological effects of apomorphine in Parkinson's disease patients are not paralleled by amino acid release changes: a microdialysis study.

We performed a microdialysis investigation of extracellular amino acid (glutamate and GABA) concentrations during sterotaxic neurosurgery (the implantation of permanent electrodes in the internal globus pallidus (GPi) or subthalamic nucleus (STN) for deep brain stimulation in advanced Parkinson's disease (PD) patients, after prolonged therapy wash-out). Electrophysiological single unit recordings and perioperative clinical status assessments were also performed. Amino acid levels were measured in the GPi and GPe (external globus pallidus) of three PD patients and in the STN of another three PD patients. Stable basal release values of the examined amino acids were obtained within one hour. In clinical "off" state, the basal levels of GABA in the GPi were double those in the GPe in all the three patients. This finding could represent a biochemical marker for GPi target identification in PD surgery. Acute subcutaneous apomorphine administration induced electrophysiological changes and clinical amelioration but did not change amino acid concentrations. This result could be due to methodological limitations of the microdialysis technique. Alternatively, it could suggest that the clinical effects of acute apomorphine might also be mediated by direct activation of dopaminergic receptors located in the output nuclei.

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