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M Raiteri

Publications and source records attributed to M Raiteri.

At least 127 records · Page 7Linked to original sources
PubMed1993

Effects of lacidipine on experimental models of atherosclerosis.

AIM: To evaluate the effect of lacidipine on the major processes of atherogenesis. METHODS: Cell-culture methods were used to study the effect of lacidipine. Low-density lipoprotein (LDL) receptor expression and cholesterol esterification were evaluated in human skin fibroblasts and in mouse peritoneal macrophages, respectively. The effect of lacidipine on cellular proliferation was tested on aortic myocytes cultured from rat aorta. RESULTS: Lacidipine did not affect LDL receptor expression, but it inhibited the ability of acetyl LDL to stimulate cholesterol esterification in macrophages by more than 95%. The drug inhibited cellular proliferation in a dose-dependent manner. This antiproliferative effect was confirmed in human femoral artery myocytes. In accord with the inhibitory effect on cellular growth, preliminary in vivo studies suggest that lacidipine may reduce neointimal formation induced by perivascular manipulation of the carotid artery in hypercholesterolemic rabbit. CONCLUSIONS: Our results indicate that lacidipine may be antiatherosclerotic through an effect on the major processes involved in atheroma formation.

Animals↗
PubMed1993

Release of cholecystokinin-like immunoreactivity in the frontal cortex of conscious rats as assessed by transcerebral microdialysis: effects of different depolarizing stimuli.

The release of cholecystokinin-like immunoreactivity (CCK-LI) from the frontal cortex of freely moving rats has been studied using a transcerebral microdialysis technique coupled to a radioimmunoassay procedure. Basal levels of CCK-LI in the dialysate were above detection limits (2.4 +/- 0.7 pg/20 min; n = 8). High-K+ media evoked CCK-LI overflow in a concentration-dependent manner. The threshold concentration was 50 mM KCl. The peak overflow evoked by 100 mM K+ amounted to 42.7 +/- 2.8 pg/20 min (n = 6); it was totally Ca2+ dependent but insensitive to 1 microM tetrodotoxin. Infusion of 4-aminopyridine (1 mM; 20 min) evoked an overflow of CCK-LI (32 +/- 2.3 pg/20 min; n = 4), which was totally Ca2+ dependent and tetrodotoxin sensitive. Depolarization with 100 micrograms/ml of veratrine (20 min) provoked a CCK-LI overflow (62.2 +/- 10 pg/20 min; n = 6), which was also blocked by tetrodotoxin or by the absence of Ca2+ ions. The CCK-LI material collected under basal conditions or during veratrine infusion consisted essentially of CCK octapeptide sulfate. The veratrine-induced CCK-LI overflow did not change significantly when the infusion time was prolonged to 100 min. A second 20-min stimulus with 100 micrograms/ml of veratrine applied 200 min after a first 20-min stimulus evoked a barely significant CCK-LI overflow. These data suggest that one single 20-min stimulus with 100 micrograms/ml of veratrine may be sufficient to deplete the CCK-LI releasable stores and that > 200 min are required to replenish the depleted CCK-containing vesicles.(ABSTRACT TRUNCATED AT 250 WORDS)

4-Aminopyridine↗
PubMed1993

Release-regulating serotonin 5-HT1D autoreceptors in human cerebral cortex.

Release-regulating 5-hydroxytryptamine (5-HT) autoreceptors in the rat brain belong to the 5-HT1B subtype. On the other hand, the human brain seems to lack 5-HT1B receptors. In the present work 5-HT autoreceptors present in human brain were characterized pharmacologically. Synaptosomes prepared from biopsy samples of human neocortex were labeled with [3H]5-HT and exposed in superfusion to selective 5-HT receptor agonists and antagonists during K+ depolarization. The rank order of potency of agonists as inhibitors of the [3H]5-HT overflow was 5-HT > sumatriptan (5-HT1D/1B) > 8-hydroxy-2-(di-n-propylamino)tetralin (5-HT1A/1D) >> 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane HCl (5-HT2/1C). The effect of 5-HT was insensitive to ketanserin (5-HT2) but antagonized by methiothepin (5-HT1/2) or by metergoline (5-HT1C/1D). The data are compatible with a classification of the human 5-HT autoreceptor as being of the 5-HT1D subtype.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1993

Glutamic acid and gamma-aminobutyric acid modulate each other's release through heterocarriers sited on the axon terminals of rat brain.

The effects of gamma-aminobutyric acid (GABA) on the spontaneous release of endogenous glutamic acid (Glu) or aspartic acid (Asp) and the effects of Glu on the release of endogenous GABA or [3H]GABA were studied in superfused rat cerebral cortex synaptosomes. GABA increased the outflow of Glu (EC50 17.2 microM) and Asp (EC50 18.4 microM). GABA was not antagonized by bicuculline or picrotoxin. Neither muscimol nor (-)-baclofen mimicked GABA. The effects of GABA were prevented by GABA uptake inhibitors and were Na+ dependent. Glu enhanced the release of [3H]GABA (EC50 11.5 microM) from cortical synaptosomes. Glu was not mimicked by the glutamate receptor agonists N-methyl-D-aspartic, kainic, or quisqualic acid. The Glu effect was decreased by the Glu uptake inhibitor D-threo-hydroxyaspartic acid (THA) and it was Na+ sensitive. Similarly to Glu, D-Asp increased [3H]GABA release (EC50 9.9 microM), an effect blocked by THA. Glu also increased the release of endogenous GABA from cortex synaptosomes. In this case the effect was in part blocked by the (RS)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione, whereas the 6-cyano-7-nitroquinoxaline-2,3-dione-insensitive portion of the effect was prevented by THA. GABA increased the [3H]D-Asp outflow (EC50 13.7 microM) from hippocampal synaptosomes in a muscimol-, (-)-baclofen-, bicuculline-, and picrotoxin-insensitive manner. The GABA effect was abolished by blocking GABA uptake and was Na+ dependent.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Transport System X-AG↗
PubMed1993

Release-regulating dopamine autoreceptors in human cerebral cortex.

Slices from fresh specimens of human neocortex which had to be removed during neurosurgery to reach subcortical tumours were labelled with [3H]-dopamine and stimulated electrically. Quinpirole, a selective dopamine D2 receptor agonist, inhibited the stimulated tritium overflow (EC50 = 25 nM; maximal inhibition: about 80% at 10 microM). The selective D1 receptor agonist, SKF 38393, was inactive up to 10 microM. Quinpirole was antagonized by the D2 receptor antagonist (-)-sulpiride (apparent pA2 = 8.26). Thus dopaminergic axon terminals in the human mesocortical pathway possess autoreceptors of the D2 type.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1993

gamma-Aminobutyric acid (GABA) autoreceptors in rat cerebral cortex and spinal cord represent pharmacologically distinct subtypes of the GABAB receptor.

gamma-Aminobutyric acid (GABA) autoreceptors regulating release of [3H]GABA have been characterized pharmacologically by using rat cerebral cortex and spinal cord synaptosomes exposed in superfusion to mild depolarization (9 mM KCl). In both regions GABA inhibited the K(+)-evoked overflow of [3H]GABA. The EC50 values amounted to 1.23 microM (cortex) and to 1.01 microM (spinal cord). Also the GABAB receptor agonist 3-aminopropylphosphonous acid (3-APPA) decreased the [3H]GABA overflow: EC50 values = 0.095 microM (cortex) and 0.078 microM (spinal cord). The classical GABAB receptor agonist (-)-baclofen was equipotent to GABA at the cortical autoreceptor (EC50 = 1.37 microM), whereas it was almost ineffective in the spinal cord (EC50 = 425 microM). (+)-Baclofen was extremely weak in both brain areas. Two GABAB receptor antagonists, phaclofen and (CGP 35348) [3-aminopropyl(diethoxymethyl)phosphinic acid] provided opposite results at the two autoreceptors examined. The IC50 values for phaclofen amounted to 47.9 microM (cortex) and to > 1000 microM (spinal cord), respectively. In contrast, CGP 35348 was almost ineffective at the cortex autoreceptors (IC50 > 300 microM), but was rather potent in the spinal cord (IC50 = 1.07 microM). To conclude, GABA autoreceptors in the cerebral cortex are classically sensitive to (-)-baclofen and to 3-APPA; they are also sensitive to phaclofen, but resistant to CGP 35348. Surprisingly, GABA autoreceptors in the spinal cord are poorly sensitive to (-)-baclofen, although they are as sensitive as the cortical autoreceptors to 3-APPA; moreover they are resistant to phaclofen, but highly sensitive to CGP 35348. The data show that pharmacologically distinct release-regulating GABAB autoreceptors exist in the central nervous system of a same animal species.

Animals↗
PubMed1993

Enhancement of glycine release from human brain cortex synaptosomes by acetylcholine acting at M4 muscarinic receptors.

Synaptosomes prepared from fresh specimens of human cerebral cortex were labeled with [3H]glycine ([3H]Gly) and distributed in parallel superfusion chambers. Exposure to 15 mM KCl evoked a tritium overflow which was largely prevented by 10 mM Mg++, suggesting a consistent component of Ca(++)-dependent [3H]Gly release. Acetylcholine (ACh; 1-100 microM), added during K(+)-depolarization, increased the release of tritium in a concentration-dependent manner (maximal effect, 60%; EC50 = 7 microM). Oxotremorine (1-100 microM) mimicked ACh. The effect of 10 microM ACh was insensitive to the nicotinic antagonist mecamylamine (100 microM), but it was blocked by the muscarinic antagonist atropine (0.1 microM). Three muscarinic receptor antagonists, pirenzepine, AF-DX 116 (11-[12-[diethylamino-methyl]-1-piperidinyl]acetyl-5-11-dihydro -6H-pyrido-[2-3-b][1,4]benzodiazepine-6-one) and himbacine, endowed with relative selectivity for various muscarinic receptor subtypes, prevented with differential affinities the effect of 10 microM ACh. Himbacine was the most potent antagonist of ACh, its pA2 (8.34) being 20- or 50-fold higher than that of pirenzepine (7.27) or AF-DX 116 (6.65). It is concluded that: 1) ACh can increase the release of Gly in human cerebral cortex; 2) the interaction occurs through muscarinic receptors which resemble most the M4 subtype; and 3) considering that Gly is required to activate the N-methyl-D-aspartate glutamate receptor, the ACh-evoked Gly release may represent a linkage between cholinergic and glutamatergic transmission, two systems strongly implicated in cognitive processes.

Acetylcholine↗
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

Pregnancy in kidney recipients under cyclosporine.

About 1 of every 50 women of child-bearing age who have a functioning kidney transplant become pregnant. Successful pregnancies following kidney allotransplantation with conventional immunosuppressive treatment are well described, and there is no evidence of abnormalities in the infants born. The use of cyclosporine (CSA) means new problems for the pregnant women and the fetus: the risk of congenital abnormalities, fetal growth retardation, hepato- and nephrotoxicity. We report the experience of 16 pregnancies in 16 of our kidney transplant patients, of which 7 were treated with CSA.

Azathioprine↗
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↗