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M Raiteri

Publications and source records attributed to M Raiteri.

At least 19 recordsLinked to original sources
PubMed1992

Effects of oxiracetam on neurotransmitter release from rat hippocampus slices and synaptosomes.

The effects of the nootropic drug oxiracetam on the K(+)-evoked overflow of [3H]D-aspartic acid ([3H]D-ASP), [3H]acetylcholine ([3H]ACh), [3H] gamma-aminobutyric acid ([3H]GABA), [3H]noradrenaline ([3H]NA) and [3H]5-hydroxytryptamine ([3H]5-HT) have been studied in superfused rat hippocampal slices. The overflow of [3H]D-ASP was enhanced by low concentrations of oxiracetam (0.01-1 microM) but not by high concentrations (10-100 microM) which showed some tendency to inhibit it. Similarly, low concentrations of oxiracetam increased, although less effectively, the depolarization-evoked overflow of [3H]ACh, whereas higher concentrations were without effect. At the concentrations active on [3H]D-ASP and [3H]ACh overflow oxiracetam did not affect that of [3H]GABA, [3H]NA or [3H]5-HT. The oxiracetam effects present in slices could not be observed in hippocampal synaptosomes. Thus oxiracetam may selectively increase the release of glutamate and acetylcholine in hippocampus by a mechanism which appears not to be sited in the releasing nerve terminals.

Acetylcholine↗
PubMed1992

Dopamine release and dopaminergic inhibition of acetylcholine release in rat striatal slices after nigro-striatal hemitransection and parenteral ganglioside administration.

Hemitransection of the nigro-striatal bundle in adult rats reduced [3H]dopamine ([3H]DA) uptake into striatal slices from the lesioned side to about 20% of that in the contralateral side 5 days after surgery. Spontaneous recovery of [3H]DA uptake was observed at days 8 and 15 post-lesion (42 and 67% of the unoperated side, respectively). After a short treatment (3 days) with the GM1 ganglioside inner ester (AGF2, 30 mg/kg i.p., daily, starting on day 2 after surgery) [3H]DA uptake amounted to 52% of that in the unoperated side. The electrically evoked fractional overflow of [3H]DA was increased by 500% in slices prepared from the lesioned side 5 days after injury, largely due to the reduced re-uptake by the DA axon terminals. The increase on day 5 was only about 350% in AGF2-treated animals. The DA D2 receptor antagonist, (-)-sulpiride, potentiated the stimulus-evoked overflow of [14C]acetylcholine in slices from the unoperated side prelabelled with [14C]choline. The effect of (-)-sulpiride was much reduced (by about 80%) in the lesioned striata at days 5 and 8 after surgery. Partial recovery was seen at day 15. The lesion did not modify the (-)-sulpiride effect in animals treated with AGF2 from the 2nd to the 5th day post-lesion. Thus early ganglioside administration slows the loss of endogenous dopaminergic control of acetylcholine release caused by partial hemitransection of the nigro-striatal bundle.

Acetylcholine↗
PubMed1992

GM1 ganglioside treatment promotes recovery of electrically-stimulated [3H]dopamine release in striatal slices from rats lesioned with kainic acid.

The electrically-evoked release of [3H]dopamine ([3H]DA) from rat striatal slices was studied after a monolateral intrastriatal injection of kainic acid (KA). The release in the KA-lesioned striatum measured 4 days after the lesion was largely reduced (by 80%) with respect to the contralateral striatum. Administration of GM1 ganglioside (GM1) beginning on the day of the lesion resulted in restoration of the catecholamine release. Significant recovery was observed when GM1 was administered i.p. daily at the dose of 3 mg/kg for 6 days. The ganglioside given for 6 days at 30 mg/kg restored to near normal the electrically-evoked [3H]DA release. Similar recovery from the KA-induced injury occurred spontaneously but required 50 days.

Animals↗
PubMed1992

Presynaptic alpha 2-adrenoceptors mediating inhibition of noradrenaline and 5-hydroxytryptamine release in rat cerebral cortex: further characterization as different alpha 2-adrenoceptor subtypes.

In a previous investigation it was suggested that the alpha 2-adrenoceptors regulating 3H-noradrenaline (3H-NA) release and the alpha 2-heteroreceptors regulating the release of 3H-5-hydroxytryptamine (3H-5-HT) from rat cerebrocortex synaptosomes represent different subtypes of the alpha 2-adrenoceptor in that (-)-mianserin potently blocked the receptors sited on 5-HT terminals but was ineffective at the autoreceptors (Raiteri et al. 1983). In this work a number of alpha 2-adrenoceptor antagonists were tested against NA as an inhibitor of the K+ (15 mmol/l)-evoked release of 3H-NA or 3H-5-HT (in presence of 1 mumol/l desipramine or citalopram, respectively) from superfused rat neocortex synaptosomes. The order of apparent affinity of the antagonists was: idazoxan greater than or equal to ORG 20769 (2-amino-4-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-thiazole-5-ca rbonitrile (Z)-2-butenedioate (1:1) salt) greater than ORG 20350 (5-chloro-4-(1-butyl-1,2,5,6-tetrahydropyridin-3-yl)-thiazole-2- amine (Z)-2-butenedioate (1:1) salt) greater than or equal to ORG 20091 (5-chloro-4-(1-methyl-1,2,5,6-tetrahydropyridin-3-yl)-thiazole-2- amine (Z)-2-butenedioate (2:1) salt) at the alpha 2-autoreceptor and idazoxan greater than or equal to ORG 20769 greater than ORG 20091 much greater than ORG 20350 at the alpha 2-heteroreceptor. Prazosin (1 mumol/l) or AR-C 239 (1 mumol/l) (2-[2-[4-(o-methoxyphenyl)piperazine-1-yl]ethyl]-4,4-dimethyl- 1,3(2H,4H)-isoquinolinedione) were ineffective in both systems.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Antagonists↗
PubMed1992

A novel endothelial-specific membrane protein is a marker of cell-cell contacts.

mAbs were raised in mice against cultured human endothelial cells (EC) and screened by indirect immunofluorescence for their ability to stain intercellular contacts. One mAb denoted 7B4 was identified which, out of many cultured cell types, specifically decorated cultured human EC. The antigen recognized by mAb 7B4 is bound at the appositional surfaces of cultured EC only as they become confluent and is stably expressed at intercellular boundaries of confluent monolayers. EC recognition specificity was maintained when the antibody was assayed by immuno-histochemistry in tissue sections of many normal and malignant tissues and in blood vessels of different size and type. The antigen recognized by 7B4 was enriched at EC intercellular boundaries similarly in vitro and in situ. In vitro, addition of mAb 7B4 to confluent EC increased permeation of macromolecules across monolayers even without any obvious changes of cell morphology. In addition, when EC permeability was increased by agents such as thrombin, elastase, and TNF/gamma IFN, its distribution pattern at intercellular contact rims was severely altered. mAb 7B4 immunoprecipitated a major protein of 140 kD from metabolically and surface-labeled cultured EC extracts which appeared to be an integral membrane glycoprotein. On the basis of its distribution in cultured cells and in tissues in situ, 7B4 antigen is distinct from other described EC proteins enriched at intercellular contacts. NH2-terminal sequencing of the antigen, immunopurified from human placenta, and sequencing of peptides from tryptic peptide maps revealed identity to the cDNA deduced sequence of a recently identified new member of the cadherin family (Suzuki, S., K. Sano, and H. Tanihara. 1991. Cell Regul. 2:261-270.) These data indicate that 7B4 antigen is an endothelial-specific cadherin that plays a role in the organization of lateral endothelial junctions and in the control of permeability properties of vascular endothelium.

Amino Acid Sequence↗
PubMed1992

gamma-Aminobutyric acid and glycine modulate each other's release through heterocarriers sited on the releasing axon terminals of rat CNS.

The ability of gamma-aminobutyric acid (GABA) and glycine (Gly) to modulate each other's release was studied in synaptosomes from rat spinal cord, cerebellum, cerebral cortex, or hippocampus, prelabeled with [3H]GABA or [3H]Gly and exposed in superfusion to Gly or to GABA, respectively. GABA increased the spontaneous outflow of [3H]Gly (EC50, 20.8 microM) from spinal cord synaptosomes. Neither muscimol nor (-)-baclofen, up to 300 microM, mimicked the effect of GABA, which was not antagonized by either bicuculline or picrotoxin. However, the effect of GABA was counteracted by the GABA uptake inhibitors nipecotic acid and N-(4,4-diphenyl-3-butenyl)nipecotic acid. Moreover, the GABA-induced [3H]Gly release was Na+ dependent and disappeared when the medium contained 23 mM Na+. The effect of GABA was Ca2+ independent and tetrodotoxin insensitive. Conversely, Gly enhanced the outflow of [3H]GABA from rat spinal cord synaptosomes (EC50, 100.9 microM). This effect was insensitive to both strychnine and 7-chlorokynurenic acid, antagonists at Gly receptors, but it was strongly Na+ dependent. Also, the Gly-evoked [3H]GABA release was Ca2+ independent and tetrodotoxin insensitive. GABA increased the outflow of [3H]Gly (EC50, 11.1 microM) from cerebellar synaptosomes; the effect was not mimicked by either muscimol or (-)-baclofen nor was it prevented by bicuculline or picrotoxin. The GABA effect was, however, blocked by GABA uptake inhibitors and was Na+ dependent. Gly increased [3H]GABA release from cerebellar synaptosomes (EC50, 110.7 microM) in a strychnine- and 7-chlorokynurenic acid-insensitive manner. This effect was Na+ dependent. The effects of GABA on [3H]Gly release seen in spinal cord and cerebellum could be reproduced also with cerebrocortical synaptosomes.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

5-Hydroxytryptamine3 receptors sited on cholinergic axon terminals of human cerebral cortex mediate inhibition of acetylcholine release.

Synaptosomes prepared from freshly obtained human cerebral cortex and labeled with [3H]choline have been used to investigate the modulation of [3H]acetylcholine ([3H]ACh) release by 5-hydroxytryptamine (5-HT). The Ca(2+)-dependent release of [3H]-ACh occurring when synaptosomes were exposed in superfusion to 15 mM KCl was inhibited by 5-HT (0.01-1 microM) in a concentration-dependent manner. The effect of 5-HT was mimicked by 1-phenylbiguanide, a 5-HT3 receptor agonist, but not by 8-hydroxy-2-(di-n-propylamino)tetralin, a 5-HT1A receptor agonist. The 5-HT3 receptor antagonists tropisetron and ondansetron blocked the effect of 5-HT, whereas spiperone and ketanserin were ineffective. It is suggested that cholinergic axon terminals in the human cerebral cortex possess 5-HT receptors that mediate inhibition of ACh release and appear to belong to the 5-HT3 type.

Acetylcholine↗
PubMed1992

Subclassification of release-regulating alpha 2-autoreceptors in human brain cortex.

1. Release-regulating alpha 2-autoreceptors in human brain were characterized pharmacologically in cortical slices from patients undergoing neurosurgery to remove subcortical tumours; the slices were prelabelled with [3H]-noradrenaline ([3H]-NA) and stimulated electrically (3 Hz, 2 ms, 24 mA) under superfusion conditions. 2. The stimulus-evoked tritium overflow was almost totally Ca(2+)-dependent and tetrodotoxin-sensitive. 3. Clonidine and oxymetazoline 0.01 to 1 microM inhibited in a concentration-dependent manner the evoked overflow of tritium. The two drugs were equipotent (EC50 = 0.03 microM) and their maximal effect was approx. 45%. Phenylephrine and methoxamine, up to 1 microM, did not affect tritium overflow. 4. Yohimbine (0.01-0.1 microM) shifted the concentration-response curve of clonidine to the right. The calculated pA2 value was 8.29. 5. Prazosin and 2-[2-[4-(o-methoxyphenyl)piperazine-1-yl]ethyl]-4,4- dimethyl-1,3(2H,4H)-isoquinolinedione (AR-C 239), tested at 0.3 microM, did not modify the concentration-response curve of clonidine. 6. The effect of clonidine was antagonized by (+)-mianserin (pA2 = 7.74), but not by up to 0.3 microM of the (-)-enantiomer. The concentration-response curve of clonidine was shifted to the right by the novel alpha 2-adrenoceptor antagonist, 5-chloro-4-(1-butyl-1,2,5,6-tetrahydropyridin-3-yl)-thiazole-2-ami ne (Z)-2-butenedioate (1:1) salt (ORG 20350) (pA2 = 7.55). 7. Yohimbine, (+)-mianserin and ORG 20350, but not prazosin and (-)-mianserin, increased the electrically-evoked tritium overflow, suggesting that autoreceptors may be tonically activated by endogenous NA. 8. Desipramine (1 microM) increased evoked tritium overflow from human cortex slices. The effect of clonidine (0.01- 1 g1M) on the evoked overflow of tritium was reduced in presence of 1 muM desipramine.9. It is proposed that autoregulation of NA release can occur in human cerebral cortex. The process involves activation of alpha 2-adrenoceptors which may be either the alpha2X or the alpha2D subtype.

Adrenergic alpha-Agonists↗
PubMed1992

Functional evidence for multiple gamma-aminobutyric acidB receptor subtypes in the rat cerebral cortex.

The aim of this work was the identification of pharmacologically distinct subtypes of gamma-aminobutyric acidB (GABAB) receptors in the central nervous system. Inasmuch as GABAB receptors are often sited on axon terminals where they mediate inhibition of transmitter release, we chose as models the GABAB receptors mediating inhibition of release of 1) endogenous GABA; 2) endogenous glutamate; and 3) somatostatin-like immunoreactivity (SRIF-LI). The experimental set up consisted of rat cerebrocortical synaptosomes depolarized in superfusion with 12 or 15 mM KCl. Endogenous GABA and glutamate were measured by high-performance liquid chromatography and SRIF-LI by radioimmunoassay. The selective GABAB receptor agonist (-)-baclofen inhibited in a concentration-dependent manner the K(+)-evoked release of GABA, glutamate and SRIF-Ll with similar potencies and efficacies [EC50 values, 1.1-1.5 microM; maximal inhibition, 45-50% at about 10 microM (-)-baclofen]. The GABAB receptor antagonist phaclofen concentration-dependently reduced the effects of (-)-baclofen on the release of GABA and SRIF-Ll but not on the release of glutamate, where it was ineffective up to 1000 microM. The rank order of potency (Ki values are shown in parentheses) are: SRIF-Ll (7.8 microM); GABA (10.4 microM); and glutamate (greater than 115 microM). The novel GABAB receptor antagonist 3-aminopropyl(diethoxymethyl) phosphinic acid (CGP 35348) displayed a different pattern on the three release systems examined (Ki values are shown in parentheses): SRIF-Ll (0.38 microM); glutamate (0.48 microM); and endogenous GABA (greater than 115 microM).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

N-methyl-D-aspartic acid (NMDA) and non-NMDA receptors regulating hippocampal norepinephrine release. III. Changes in the NMDA receptor complex induced by their functional cooperation.

N-methyl-D-aspartic acid (NMDA) and non-NMDA ionotropic receptors mediating increase of norepinephrine (NE) release coexist on NE rat hippocampus axon terminals. Activation of non-NMDA receptors permits activation of NMDA receptors also in presence of Mg++ ions and induces important changes in the NMDA receptor recognition site and in its intrinsic ion channel. We have now studied the effects of this receptor-receptor interaction on the glycine site of the NMDA receptor by using two antagonists, 7-chloro-kynurenic acid and (+-)-3-amino-1-hydroxy-2-pyrrolidone (HA-966). Both the [3H]NE releases induced from rat hippocampus synaptosomes by NMDA (no Mg++ added) and by NMDA+quisqualic acid (QA), in the presence of 1.2 mM Mg++, were prevented by 7-chloro-kynurenic acid with almost identical potency (IC50 values: 0.19 and 0.39 microM, respectively). In contrast, HA-966, up to 1000 microM, was ineffective toward NMDA (no Mg++), but it blocked the effect of NMDA + QA in presence of Mg++ (IC50 = 1.1 microM). HA-966 also antagonized NMDA + QA in Mg(++)-free medium. Thus coactivation of non-NMDA and NMDA receptors seems to permit the antagonistic activity of HA-966. In the presence of Mg++, L-glutamic acid (L-Glu) enhanced [3H]NE release. The sensitivity of the L-Glu effect to various antagonists was similar to that of the effect of NMDA + QA, indicating that the NMDA receptor complex activated either by NMDA + QA or by the physiological transmitter L-Glu in presence of Mg++ ions undergoes dramatic conformational changes at the recognition site, at the ion channel as well as at the glycine site.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed1992

N-methyl-D-aspartic acid (NMDA) and non-NMDA receptors regulating hippocampal norepinephrine release. I. Location on axon terminals and pharmacological characterization.

UNLABELLED: The effects of endogenous and exogenous agonists at excitatory amino acid receptors mediating enhancement of [3H]norepinephrine [( 3H]NE) release have been investigated using superfused rat hippocampal synaptosomes. In Mg(++)-free medium L-glutamic acid (L-Glu), L-aspartic acid (L-Asp), N-methyl-D-aspartic acid (NMDA), kainic acid, (RS)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and quisqualic acid (QA) all increased the release of [3H]NE. L-Glu produced the largest effect. In the presence of Mg++ (1.2 mM), the effect of L-Glu decreased by about 40%; L-Asp and NMDA lost completely their activity while the effects of kainic acid, QA and AMPA did not change significantly. Similarly to NMDA, the effect of L-Asp was augmented by glycine and blocked by NMDA receptor antagonists, while it was insensitive to the non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). The effect of L-Glu on [3H] NE release was partly decreased by the NMDA receptor channel blocker (+)-5-methyl-10,11-dihydro-5-H-dibenzo[a,d]cycloepten-5,10-imine (MK-801) and partly by CNQX; when present together, the two antagonists completely abolished the L-Glu effect. The QA enhancement of [3H]NE release was antagonized by CNQX but it was insensitive to other classical non-NMDA receptor antagonists. IN CONCLUSION: 1) release-enhancing NMDA and non-NMDA receptors exist on noradrenergic axon terminals of rat hippocampus; 2) L-Asp appears to be a potent selective NMDA receptor agonist while L-Glu can activate also non-NMDA receptors; 3) the NE-releasing receptor activated by QA may represent a QA/AMPA receptor subtype.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed1992

N-methyl-D-aspartic acid (NMDA) and non-NMDA receptors regulating hippocampal norepinephrine release. II. Evidence for functional cooperation and for coexistence on the same axon terminal.

The possible interactions between activation of N-methyl-D-aspartic acid (NMDA) receptors and non-NMDA receptors regulating the release of [3H]norepinephrine [( 3H]NE) have been investigated in superfused synaptosomes from rat hippocampus. NMDA--at a concentration (100 microM) which, in a medium containing 1.2 mM Mg++ ions, did not evoke [3H]NE release--acquired releasing activity in the presence of equimolar concentrations of quisqualic acid (QA), (RS)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) or kainic acid. The [3H] NE release evoked by NMDA plus QA in the presence of Mg++ ions was Ca(++)-dependent, partly tetrodotoxin-sensitive, inhibited by clonidine but insensitive to desipramine. The NMDA receptor antagonists D-2-amino-5-phosphonopentanoic acid (D-AP5) and (+)-5-methyl-10,11-dihydro-5-H-dibenzo[a,d]cycloepten-5,10-imine (MK-801) antagonized the NMDA-induced [3H]NE release in Mg(++)-free medium; the IC50 values amounted, respectively, to 81.4 microM and to 1.11 microM. When NMDA was tested in the presence of QA and Mg++ ions, the affinity of D-AP5 was enormously increased (IC50 = 40 nM; i.e., more than 6 orders of magnitude); the affinity of MK-801 was found to be augmented by 350-fold.(ABSTRACT TRUNCATED AT 250 WORDS)

2-Amino-5-phosphonovalerate↗
PubMed1991

5-HT2 presynaptic receptors mediate inhibition of glutamate release from cerebellar mossy fibre terminals.

'Giant' synaptosomes originating from mossy fibre terminals and having sedimentation properties different from those of standard synaptosomes were obtained from rat cerebellum. Exposure of superfused giant synaptosomes to 15 mM KCl caused the release of endogenous glutamate in a largely (about 80%) calcium-dependent manner. The K(+)-evoked overflow of glutamate was inhibited in a concentration-dependent manner by 5-hydroxytryptamine (5-HT) and by the 5-HT2 receptor agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane HCl (DOI), but not by the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT). The effects of 5-HT and DOI were quite potent, already reaching significant inhibition (about 25%) at 10 nM. The 5-HT2 receptor antagonist ketanserin counteracted the inhibitory effect of 5-HT. In cerebellar slices, ketanserin increased on its own the calcium-dependent K(+)-evoked release of glutamate and this effect was not prevented by tetrodotoxin (TTX). The results support the idea that cerebellar mossy fibres use glutamate as a transmitter and show that the release of glutamate can be inhibited via presynaptic heteroreceptors of the 5-HT2 type probably localized on the mossy fibre terminals.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1991

Cholinergic nerve terminals of human cerebral cortex possess a GABA transporter whose activation induces release of acetylcholine.

The effect of gamma-aminobutyric acid (GABA) on the release of [3H]acetylcholine [( 3H]ACh) from human cerebral cortex nerve terminals was investigated using synaptosomes prepared from neurosurgical specimens (which had to be removed to reach deeply located tumors) prelabeled with [3H]choline and exposed in superfusion to varying concentrations of GABA. The amino acid (3-100 microM) increased in a concentration-dependent manner (maximal effect: 40%; EC50 = 14.7 microM) the release of [3H]ACh but not that of [3H]choline. The GABAA receptor agonist muscimol (up to 100 microM) did not increase significantly the release of [3H]ACh. Accordingly, the effect of GABA was insensitive to the GABAA receptor antagonist bicuculline. The release of [3H]ACh was not affected by the GABAB receptor agonist (-)-baclofen (100-300 microM). The GABA-induced [3H]ACh release was counteracted by two inhibitors of GABA uptake, N-(4,4-diphenyl-3-butenyl)nipecotic acid (SKF 89976A) and nipecotic acid. Moreover, the enhancing effect of GABA on [3H]ACh release was clearly Na+-dependent and was reduced by almost 90% in presence of 23 mM NaCl. The data indicate that, similarly to what had been observed in the rat, cholinergic nerve terminals in the human cerebral cortex possess a GABA transporter. Activation of this carrier brings about release of newly synthesized ACh. GABA and ACh might co-exist in some cerebrocortical nerve endings in the vertebrate brain, including man.

Acetylcholine↗