Serotonin-glutamate interaction in rat cerebellum: involvement of 5-hydroxytryptamine receptor subtypes.
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8-Hydroxy-2-(di-n-propylamino)tetralin↗
Biomedical subjects
M Raiteri
Publications and source records attributed to M Raiteri.
[Echography in the study of thoracic pathology. II-- Guided biopsy].
The usefulness of ultrasonic studies for guiding the needle during biopsy of solid lesions or evacuation of saccate effusions and empyemas. Is a explained possible diagnostic protocol is then proposed which includes the ultrasonic examination in the diagnostic approach to parietal, mediastinic or diaphragmatic lesions.
Biopsy↗
Studies on [3H]GABA and endogenous GABA release in rat cerebral cortex suggest the presence of autoreceptors of the GABAB type.
The presence of autoreceptors for gamma-aminobutyric acid (GABA) in the CNS was reinvestigated using rat cortex synaptosomes prelabeled with [3H]GABA and exposed to GABA by superfusion in the presence of a new GABA uptake inhibitor, N-(4,4-diphenyl-3-butenyl)-nipecotic acid (SK&F 89976A). This compound itself did not increase the basal or the depolarization-evoked release of [3H]GABA. GABA reduced in a concentration-dependent way the release of [3H]GABA evoked by 15 mM K+. The effect was not antagonized by bicuculline, picrotoxin or by the new GABAA antagonist SR 95531. The GABAA agonist muscimol did not affect [3H]GABA release. This was reduced by (-)baclofen (but not by the (+) isomer) and the concentration-inhibition curve of (-)baclofen was superimposable on to that of GABA. Also the K+-evoked release of endogenous GABA was stereoselectively and concentration dependently inhibited by the (-) enantiomer of baclofen. It is concluded that the release of GABA from rat cortical nerve endings may be inhibited through the activation of autoreceptors which appear to belong to the GABAB type.
Animals↗
GABAergic nerve terminals in rat hippocampus possess alpha 2-adrenoceptors regulating GABA release.
Noradrenaline enhanced in a concentration-dependent way the basal release of endogenous GABA from superfused rat hippocampus synaptosomes. The alpha 2-adrenoceptor antagonist yohimbine prevented the releasing effect of noradrenaline while the alpha 1-adrenoceptor antagonist prazosin was ineffective. It is concluded that GABAergic nerve terminals in rat hippocampus possess adrenoceptors of the alpha 2-subtype whose activation causes enhancement of GABA release.
Animals↗
Carriers for GABA and noradrenaline uptake coexist on the same nerve terminal in rat hippocampus.
gamma-Aminobutyric acid (GABA; 1-300 microM) increased the basal release of [3H]noradrenaline ([3H]NA) from rat hippocampal synaptosomes. The effect of GABA at low concentrations (below 10 microM) was largely bicuculline-sensitive while the sensitivity to bicuculline decreased at higher concentrations. Muscimol mimicked GABA but only below 10 microM; bicuculline antagonized the effect of muscimol. Up to 300 microM (-)baclofen did not modify [3H]NA release. The effect of GABA was potently counteracted by SK & F 89976A, SK & F 100330A and SK & F 100561, three novel inhibitors of neuronal GABA uptake. These compounds could not entirely prevent the effect of GABA, being least effective at the lowest GABA concentrations (below 10 microM) and becoming progressively more effective when the concentrations of GABA were increased. The effect of muscimol was insensitive to SK & F 89976A. The effect of 100 microM GABA was totally prevented when bicuculline and uptake inhibitor were added together to the superfusion medium. The results suggest that the basal release of [3H]NA can be enhanced by GABA through two mechanisms: GABAA receptor activation and penetration into NA terminals by a GABA uptake process. Thus a carrier for the uptake of NA and a carrier for the uptake of GABA appear to coexist on the same nerve terminal in rat hippocampus.
Animals↗
Vasoactive intestinal polypeptide (VIP) potentiates the muscarinic stimulation of phosphoinositide turnover in rat cerebral cortex.
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Acetylcholine↗
Is the muscarinic receptor that mediates potentiation of dopamine release negatively coupled to the cyclic GMP system?
Dopamine (DA) terminals in rat corpus striatum and frontal cortex possess muscarinic receptors that mediate enhancement of the depolarization-evoked release of the catecholamine. The effects of the membrane-permeating cyclic guanosine monophosphate (cyclic GMP) analog 8-Br-cyclic GMP and of the phosphodiesterase inhibitor isobutylmethylxanthine (IBMX) on the muscarinic-induced increase of DA release were investigated in striatal synaptosomes prelabeled with [3H]DA and exposed in superfusion to 15 mM KCl and to acetylcholine (ACh). Preincubation of synaptosomes with 8-Br-cyclic GMP (10-200 microM) or with IBMX (200 microM) prevented the ACh-induced enhancement of [3H]DA release, without affecting the K+-evoked release of the [3H]amine. No significant decrease of the ACh effect was observed when 8-Br-cyclic GMP or IBMX were added concomitantly with ACh to the superfusion medium. The data suggest that stimulation of presynaptic muscarinic receptors on DA terminals may produce enhancement of 3H DA release through a decrease of the intraterminal cyclic GMP content.
1-Methyl-3-isobutylxanthine↗
Release-regulating GABAA receptors are present on noradrenergic nerve terminals in selective areas of the rat brain.
The effects of gamma-aminobutyric acid (GABA) on the spontaneous release of [3H]-norepinephrine ([3H]-NE) were investigated by means of superfused synaptosomes prepared from different areas of the rat brain and prelabeled with [3H]-NE. GABA increased in a concentration-dependent way (1-300 microM) the release of [3H]-NE in hippocampal synaptosomes. The effect of GABA was mimicked in part by muscimol. Similar effects were observed in cerebral cortex synaptosomes where GABA and muscimol were however less potent than in hippocampus. No effect could be observed in hypothalamic synaptosomes. Bicuculline antagonized the effect of muscimol and that of low concentrations of GABA (below 10 microM). Above 10 microM, the [3H]-NE releasing effects of GABA became progressively less sensitive to bicuculline. (-)-Baclofen did not affect the spontaneous release of [3H]-NE. It is concluded that release-regulating receptors of the GABAA subtype are present on NE nerve terminals in selective areas of the rat brain.
Animals↗
Choline increases endogenous GABA release in rat hippocampus by a mechanism sensitive to hemicholinium-3.
The effects of choline (Ch) on the spontaneous release of endogenous gamma-aminobutyric acid (GABA) and of 3H-GABA were studied in superfused rat hippocampal synaptosomes. Choline enhanced in a concentration-dependent way the release of endogenous GABA but did not affect that of the radioactive aminoacid. The effect of Ch was not antagonized by atropine or mecamylamine; moreover, it was not mimicked by acetylcholine, oxotremorine or carbachol. The Ch-induced GABA release was counteracted by hemicholinium-3. Thus the release of endogenously synthesized GABA (but not that of the aminoacid taken up) may be regulated by Ch through a mechanism involving penetration into the releasing terminal through a Ch uptake system.
Acetylcholine↗
Interaction between 5-HT uptake inhibition and activation of 5-HT autoreceptors by exogenous agonists in rat cerebral cortex slices and synaptosomes.
Rat cerebral cortex slices or synaptosomes were labelled with 3H-5-hydroxytryptamine (3H-5-HT) and subsequently superfused. They were depolarized by electrical stimulation (slices) or with high K+ (slices and synaptosomes). Continuous electrical stimulation (2 Hz, 24 mA, 2 ms) and continuous or discontinuous K+ depolarization (15-25 mM) were used. 1. Continuous electrical stimulation or continuous K+-depolarization of slices evoked a steady overflow of tritium that slowly decayed with time. 2. Exposure to increasing concentrations of 5-methoxy-3(1,2,3,6-tetrahydropyridin-4-yl)-1H-indole succinate (RU 24969) (0.001-0.1 microM) during continuous electrical stimulation produced a concentration-dependent decrease in tritium overflow. Citalopram (1 microM) counteracted the effect of RU 24969. 3. RU 24969 inhibited the evoked 3H-overflow and citalopram reduced the effect of RU 24969 also during continuous depolarization of slices with 20 mM K+. Similar results were obtained by using 5-methoxytryptamine or LSD. 4. In slices 1 microM citalopram increased significantly the tritium overflow evoked by electrical stimulation or by 20 mM K+-depolarization. 5. Increasing the K+ concentration from 20 mM to 25 mM mimicked the effects of 1 microM citalopram both on the RU 24969 activity and on the evoked tritium overflow. 6. RU 24969 (0.001-0.1 microM) decreased in a concentration-dependent way the release of tritium from cortical synaptosomes depolarized with K+ (15-20 mM). The presence of 1 microM citalopram did not modify significantly the effect of the agonist. Citalopram was ineffective also when the serotonin uptake carrier in superfused synaptosomes was activated by tryptamine.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
A carrier for GABA uptake exists on noradrenaline nerve endings in selective rat brain areas but not on serotonin terminals.
UNLABELLED: gamma-Aminobutyric acid (GABA) increased in a concentration-dependent way (3-300 microM) the basal release of tritium from rat cerebral cortex and hippocampus synaptosomes, prelabelled with 3H-noradrenaline (3H-NA); however, GABA was ineffective on hypothalamic nerve endings. The effect displayed by low concentrations (less than 10 microM) of GABA was largely bicuculline-sensitive. Muscimol mimicked GABA, while (-)baclofen was inactive. The releasing effects produced by concentrations of GABA higher than 10 microM were largely prevented by SK&F89976A, SK&F100330A and SK&F100561, three novel GABA uptake inhibitors. When present together, GABA uptake blocker and bicuculline counteracted entirely the GABA effects. The basal release of 3H-5-hydroxytryptamine (3H-5-HT) in synaptosomes from various CNS regions was not affected by GABA. IN CONCLUSION: GABA can enhance 3H-NA release not only through GABA-A receptors but also by penetrating into NA terminals through a GABA uptake system. This implies coexistence of carriers for NA and GABA uptake on a same nerve terminal. The carrier coexistence occurs in selective CNS areas. The phenomenon appears to be transmitter-selective.
Animals↗
(-)-Propranolol and (+/-)-cyanopindolol are mixed agonists-antagonists at serotonin autoreceptors in the hippocampus of the rat brain.
The effects of (-)-propranolol, (+)-propranolol and (+/-)-cyanopindolol on the release of [3H]5-hydroxytryptamine [( 3H]5-HT) were investigated in synaptosomes from the hippocampus of the rat, depolarized in superfusion with 15 mM KCl. (-)-Propranolol, but not (+)-propranolol, inhibited in a concentration-dependent way the K+-evoked release of [3H]5-HT. (+/-)-Cyanopindolol behaved similarly but was about 10 times more potent than (-)-propranolol. The inhibitory effects of (-)-propranolol and (+/-)-cyanopindolol were prevented by the autoreceptor antagonist methiothepin. Both beta-adrenoceptor antagonists antagonized the inhibition by exogenous 5-HT of the K+-evoked release of [3H]5-HT. The data suggest that some beta-adrenoceptor antagonists may behave as mixed agonists-antagonists at the 5-HT autoreceptor. Synaptosomes in superfusion appear to be particularly suitable to study separately agonistic compared to antagonistic activity of compounds having a mixed agonist-antagonist profile.
Animals↗
Release in vitro as a model to study neurotransmitter receptors.
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Animals↗
Regional selectivity of a gamma-aminobutyric acid-induced [3H]acetylcholine release sensitive to inhibitors of gamma-aminobutyric acid uptake.
The effects of gamma-aminobutyric acid (GABA) on the release of [3H]acetylcholine ([3H]ACh) were studied in synaptosomes prepared from rat hippocampus, cerebral cortex, hypothalamus, and striatum and prelabelled with [3H]choline. When synaptosomes were exposed in superfusion to exogenous GABA (0.01-0.3 mM) the basal release of newly synthesized [3H]ACh was increased in a concentration-dependent way in hippocampus, cortex, and hypothalamus nerve endings. In contrast, the release of [3H]ACh was not significantly affected by GABA in striatal synaptosomes. The effect of GABA was not antagonized significantly by bicuculline or picrotoxin. Muscimol caused only a slight not significant increase of [3H]ACh release when tested at 0.3 mM whereas, at this concentration, (-)-baclofen was totally inactive. The GABA-induced release of [3H]ACh was counteracted by SKF 89976A, SKF 100561, and SKF 100330A, three strong and selective GABA uptake inhibitors. The data suggest that, in selective areas of the rat brain, GABA causes release of [3H]ACh following penetration into cholinergic nerve terminals through a GABA transport system.
Acetylcholine↗
[3]Pirenzepine binding in rat corpus striatum decreases after hemitransection of the nigro-striatal pathway.
The localization and pharmacologic characterization of muscarinic receptors possibly regulating the release of dopamine (DA) in rat corpus striatum were investigated by in vitro binding with [3H]pirenzepine ([3H]PZ) after hemitransection of the nigro-striatal pathway. DA levels in the corpus striatum ipsilateral to the lesion were substantially reduced by 66% compared with the unlesioned side after 8 days. The uptake of [3H]DA was also diminished by 63%. A significant decrease in the specific binding of [3H]PZ of 42% was seen in the corpus striatum ipsilateral to the lesion. The data indicate a loss of binding sites, whereas the lesion caused no change in the affinity constant for the muscarinic antagonist. The results support those previously obtained in studies of the muscarinic modulation of [3H]DA release from striatal synaptosomes and favor the idea that at least part of the muscarinic receptors regulating striatal DA release are localized on the nigro-striatal axon terminals and belong to the pirenzepine-sensitive subtype.
Animals↗
Coexistence of carriers for dopamine and GABA uptake on a same nerve terminal in the rat brain.
The ability of gamma-aminobutyric acid (GABA) to affect the release of [3H]-dopamine in rat brain synaptosomes prepared from corpus striatum, frontal cortex and hypothalamus and prelabelled with the radioactive catecholamine in the presence of desipramine was examined. GABA (10-300 microM) increased in a concentration-dependent way the basal release of [3H]-dopamine from striatum and cortical synaptosomes; however, its effect was much less pronounced in hypothalamic nerve terminals. 2,4-Diaminobutyric acid (DABA) mimicked GABA although less potently. Neutral amino acids such as leucine, valine or alpha-aminoisobutyric acid (100-300 microM) did not affect or increased minimally the release of [3H]-dopamine. The GABA-induced [3H]-dopamine release was not prevented by the GABAA-receptor antagonists, bicuculline or picrotoxin. The GABAA-receptor agonist, muscimol (10-300 microM), displayed only a very weak, not significant, enhancing effect on [3H]-dopamine release. The GABAB-receptor agonist (-)-baclofen (100 or 300 microM) had no effect. Three novel and selective inhibitors of GABA uptake, N-(4,4-diphenyl-3-butenyl)-nipecotic acid (SK&F 89976A), N-(4,4-diphenyl-3-butenyl)-guvacine (SK&F 100330A) and N-(4,4-diphenyl-3-butenyl)-homo-beta-proline (SK&F 100561) potently counteracted the enhancing effect of GABA on [3H]-dopamine release. Nipecotic acid also reduced the effect of GABA. It is concluded that carriers for the uptake of dopamine and GABA may coexist on the same nerve terminal in the rat brain.
Aminobutyrates↗
Presence of a gamma-aminobutyric acid (GABA) uptake system on cholinergic terminals of rat hippocampus: evidence for neuronal coexistence of acetylcholine and GABA?
The effect of gamma-aminobutyric acid (GABA) on the basal release of [3H]acetylcholine ([3H]ACh) was investigated using synaptosomes prepared from rat hippocampus and superfused after prelabeling with [3H]choline. Exogenous GABA added to the superfusion medium caused a long-lasting and concentration-dependent enhancement of the basal efflux of [3H]ACh. The effect of GABA was not antagonized by bicuculline or picrotoxin. Muscimol increased slightly but not significantly the release of [3H]ACh, whereas (+/-)-baclofen or (-)-baclofen were ineffective. The effect of GABA was counteracted by SK&F 89976A [N-(4,4-diphenyl-3-butenyl)-nipecotic acid], SK&F 100330A [N-(4,4-diphenyl-3-butenyl)-guvacine] and SK&F 100561 [N-(4,4-diphenyl-3-butenyl)-homo-beta-proline], three novel inhibitors of GABA uptake, but was unaffected by hemicholinium-3 or by beta-alanine. Nipecotic acid, a substrate-inhibitor of the GABA transporter, mimicked GABA and enhanced [3H]ACh release. The results indicate that a GABA transport system is present on cholinergic terminals.
Acetylcholine↗
GABA enhances acetylcholine release from hippocampal nerve endings through a mechanism blocked by a GABA uptake inhibitor.
The effect of gamma-aminobutyric acid (GABA) on the release of [3H]acetylcholine [( 3H]ACh) was investigated using superfused rat hippocampal synaptosomes. GABA enhanced the basal efflux of [3H]ACh. The effect of GABA was bicuculline-insensitive. Muscimol, (+/-)-baclofen or (-)-baclofen did not increase [3H]ACh release. The effect of GABA was counteracted by SK&F 89976 A (N-(4,4-diphenyl-3-butenyl)-nipecotic acid), a GABA uptake inhibitor. One possible interpretation of the results is that a GABA transport system is present on cholinergic terminals, suggesting that GABA and ACh may coexist in some rat hippocampus nerve endings. Another possibility is that the effect of GABA is mediated by a novel subtype of GABA receptor sensitive to SK&F 89976 A.
Acetylcholine↗