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Biomedical subjects

G Bonanno

Publications and source records attributed to G Bonanno.

At least 127 records · Page 7Linked to original sources
PubMed1987

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↗
PubMed1987

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↗
PubMed1987

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↗
PubMed1987

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↗
PubMed1987

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↗
PubMed1987

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↗
PubMed1987

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↗
PubMed1986

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↗
PubMed1986

Pharmacological characterization of release-regulating serotonin autoreceptors in rat cerebellum.

The release of [3H]5-hydroxytryptamine ([3H]5-HT) evoked by 15 mM KCl in superfused rat cerebellum synaptosomes was inhibited by 5-HT (pEC30 = 8.73). Methiothepin antagonized 5-HT (pA2 = 9.28); ketanserin, methysergide, cinanserin and spiperone were ineffective. The receptors involved were activated (pEC30 = 8.90) by the 5-HT1 agonist 5-methoxy-3-[1,2,3,6-tetrahydropyridin-4-yl]-1H-indole (RU 24969) X (-)Propranolol shifted to the right (pA2 = 8.05) the dose-response curve of 5-HT. The 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) was ineffective. In conclusion, autoreceptors are present on 5-HT nerve endings in rat cerebellum and appear to belong to the 5-HT1B subtype.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1986

Autoreceptors and alpha 2-adrenoceptors at the serotonergic axons of rabbit brain cortex.

Slices of the rabbit occipito-parietal cortex were preincubated with 3H-serotonin and then superfused and stimulated electrically (2 min at 3 Hz). In the absence of drugs, the stimulation-evoked overflow of tritium was approximately 3% of the tritium content of the tissue. Unlabelled serotonin and 5-carboxamido-tryptamine, when administered in the presence of 6-nitroquipazine, reduced the evoked overflow of tritium. Their effects were antagonized by metitepin (apparent pA2 value 8.1) and (+/-)-cyanopindolol (apparent pA2 value 6.4). Metitepin, but not cyanopindolol, increased evoked tritium overflow; the effect of metitepin was greater in the presence than in the absence of nitroquipazine. The evoked overflow of tritium was also depressed by clonidine, an effect antagonized by idazoxan (apparent pA2 value 7.0) but not by prazosin. Phenylephrine caused a decrease only at high concentrations that simultaneously accelerated basal tritium efflux. Prazosin and idazoxan did not change evoked tritium overflow, and phentolamine increased it significantly only when administered in the presence of (+)-oxaprotiline. Rauwolscine produced an inhibition that was prevented by metitepin. It is concluded that the serotonergic axons of the rabbit occipitoparietal cortex possess presynaptic, release-inhibiting serotonin autoreceptors and alpha 2-adrenoceptors. The receptors appear to receive an input of endogenous serotonin and, to a lesser extent, noradrenaline, under the conditions of these in vitro experiments.

Adrenergic alpha-Agonists↗
PubMed1986

Differential pharmacology and function of two 5-HT1 receptors modulating transmitter release in rat cerebellum.

The release of endogenous glutamate (GLU) elicited by depolarization of rat cerebellum synaptosomes was inhibited potently (pEC30 = 9.77) by 5-hydroxytryptamine (5-HT). The 5-HT action was antagonized by methiothepin (pA2 = 10.37); ketanserin, methysergide, cinanserin and spiperone were ineffective. Exogenous 5-HT also inhibited the release of [3H]-5-HT from cerebellar synaptosomes (pEC30 = 8.73). Methiothepin, but not ketanserin, methysergide, cinanserin or spiperone counteracted the inhibition (pA2 = 9.28). The receptors involved (presynaptic 5-HT heteroreceptors and autoreceptors) were activated by the 5-HT1 agonist RU 24969 (5-methoxy-3-[1,2,3,6-tetrahydropyridin-4-yl]-1H-indole) which showed comparable activity at the two receptor systems. (-)-Propranolol, used as a 5-HT1 antagonist, shifted to the right (pA2 = 8.05) the dose-response curve of 5-HT at the autoreceptors, but was ineffective at the receptors regulating GLU release. On the contrary, the 5-HT1A agonist 8-hydroxy-2-di-N-propylamino)tetralin activated the presynaptic heteroreceptors (pEC30 = 7.98), but was ineffective as a 5-HT autoreceptor agonist. The results allow the following major conclusions: 5-HT receptors are located on GLU terminals in rat cerebellum where they may modulate in an inhibitory way the release of GLU; 5-HT autoreceptors possibly involved in a negative feedback regulation of 5-HT release are present on cerebellar 5-HT nerve endings; 5-HT autoreceptors and heteroreceptors can be pharmacologically differentiated and appear to represent subtypes of the 5-HT1 receptor.(ABSTRACT TRUNCATED AT 250 WORDS)

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1985

Chronic clonidine induces functional down-regulation of presynaptic alpha 2-adrenoceptors regulating [3H]noradrenaline and [3H]5-hydroxytryptamine release in the rat brain.

Clonidine inhibited, through the activation of alpha 2 presynaptic receptors, the release of [3H]noradrenaline (pIC30 = 7.47) and [3H]5-hydroxytryptamine (pIC30 = 6.47) evoked by 15 mM KCl from superfused rat cerebral cortex synaptosomes. The natural agonist noradrenaline inhibited the K+-evoked release of the two [3H]amines less effectively after long-term (12 days) treatment with clonidine than after acute treatment. It can be concluded that chronic clonidine administration can induce down-regulation of both the alpha 2 presynaptic autoreceptors located on noradrenaline terminals and the alpha 2 presynaptic heteroreceptors located on serotonin terminals.

Animals↗
PubMed1985

Activation of muscarinic receptors on striatal synaptosomes increases the release of endogenous dopamine.

The release of endogenous dopamine was investigated using rat striatal synaptosomes in superfusion. Depolarization with 15 mM KC1 evoked a release which was totally calcium-dependent. Also, the basal release of dopamine was in part dependent on the presence of calcium ions. Exogenous acetylcholine potentiated the K+-induced release of endogenous dopamine through the activation of receptors of the muscarinic type located on dopamine nerve terminals. Very similar results were obtained when the release of 3H-dopamine, previously taken up into striatal synaptosomes, was examined.

Acetylcholine↗
PubMed1984

Is there a functional linkage between neurotransmitter uptake mechanisms and presynaptic receptors?

The possibility of interaction between neurotransmitter uptake mechanisms and presynaptic receptors regulating transmitter release was investigated using rat brain synaptosomes in superfusion. Various conditions were considered including: absence of substrate for the uptake with uptake potentially operative; absence of substrate and presence of uptake inhibitors; and uptake activated by added substrate, with or without uptake inhibitors. The release of [3H]-5-hydroxytryptamine ([3H]-5-HT) evoked by 15 mM KCl from cerebral cortex synaptosomes was inhibited by lysergic acid diethylamide. The 5-HT uptake inhibitors citalopram and chlorimipramine did not affect the inhibitory action of lysergic acid diethylamide. Clonidine decreased both the K+-evoked release of [3H]norepinephrine and that of [3H]-5-HT in cortical synaptosomes through the activation of presynaptic alpha-2 adrenoceptors. In superfusion conditions, the action of clonidine on [3H]norepinephrine release was not antagonized by the norepinephrine uptake inhibitors desipramine or cocaine; similarly, the inhibition of [3H]-5-HT release was unaffected when 5-HT uptake was blocked. The K+-evoked release of [3H]dopamine from striatal nerve terminals was potentiated by acetylcholine (ACh) through the activation of muscarinic presynaptic receptors. The action of ACh was not modified by the presence of nomifensine, a dopamine uptake inhibitor. Finally, in superfused cortical synaptosomes, the block of the high-affinity uptake of choline by hemicholinium-3 had no effect on the muscarinic autoreceptor-mediated inhibition of [3H]ACh release by ACh. Altogether the present results do not support the previously proposed idea that in nerve terminals a functional coupling may exist between uptake mechanisms and presynaptic receptors.

Acetylcholine↗
PubMed1983

Immunological imbalance in uncomplicated chronic alcoholism.

The lymphocyte response to unspecific mitogenic lectins and the frequency of the lymphocytary populations and two subpopulations (DR- and Fc gamma-positive T-cells) as well as the serum immunoglobulin levels were tested. Blood samples were drawn from 15 volunteers with chronic alcoholism, an no clinical detectable correlated diseases and from 8 healthy subjects as controls. An activation of the immune system was found, characterized by an increase of T lymphocytes, DR-positive T-cells, IgA and IgG. Aspects of this activation are discussed.

Adult↗
PubMed1983

[Pathology caused by suture materials in patients with gastric resection. Endoscopic findings].

The authors report the results obtained from an endoscopic study on 131 gastric resected patients, who in 18.3% showed a pathology due to suture thread. The Authors dwell upon the clinical picture shown by these patients, and also consider the cases performed on urgency for hematemesis and/or melaena, and upon the diagnostical role of endoscopy. Moreover, they report the results obtained through the endoscopic therapy, which in 100% of the cases allowed the removal of the suture thread.

Adult↗