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M Di Luca

Publications and source records attributed to M Di Luca.

69 records · Page 4Linked to original sources
PubMed1992

The phosphorylation state of DARPP-32, a third messenger for dopamine, is regulated by in vivo pharmacological treatments.

It has been recently proposed that DARPP-32 participates, as third messenger, in the mediation of effects induced by dopamine at the cellular level. DARPP-32 is indeed localized almost exclusively on dopaminoceptive neurons bearing the D1 receptor subtype and it is phosphorylated by cAMP-dependent protein kinase. In its phospho-form, DARPP-32 acts as an inhibitor of protein phosphatase-1. In vivo pharmacological treatment with selective D1 agonists and antagonists induces changes in the phosphorylation state of DARPP-32 that can be correlated to changes in cAMP, mediated in turn by D1 and D2 receptors. These data demonstrate that the measurement of the phosphorylation state of DARPP-32 with the back-phosphorylation assay can represent a useful biochemical tool to gain further insight into the sequence of events elicited by specific dopaminergic drugs in vivo.

Animals↗
PubMed1991

Microencephaly reduces the phosphorylation of the PKC substrate B-50/GAP43 in rat cortex and hippocampus.

The administration of the antimitotic agent methylazoxymethanol (MAM) to rats at day 15 of gestation results in a consistent loss of intrinsic neurons primarily in cortex and hippocampus. These animals when adult, show a cognitive impairment, if tested in specific behavioural tasks. B-50/GAP43 is a neuronal phosphoprotein, specific substrate for protein kinase C (PKC) and involved in the development and plasticity of synaptic connections. Since B-50/GAP43 has been implicated in functional modulation of synapses and in the molecular mechanism underlying cognitive processes, we studied the phosphorylation of B-50 in cortex and hippocampus of control and MAM-treated rats. Here we report that B-50 in MAM-treated rats shows a marked reduction in the phosphate incorporation in the areas affected by the prenatal treatment. In situ hybridization studies demonstrate that the mRNA levels for B-50 are not altered in MAM-treated rats and that the relative amount of the protein, as revealed by Western blot analysis, is also not affected in microencephalic rats. These results suggest that microencephalic animals might represent a useful experimental model to study biochemical correlates of cognitive impairment and synaptic plasticity.

Animals↗
PubMed1990

Beta-adrenoceptor desensitization induced by antigen challenge in guinea-pig trachea.

As beta-adrenoceptor function in the lung could be relevant in asthma, we carried out a functional and biochemical study of the possible occurrence of beta-receptor desensitization after the anaphylactic reaction induced in vitro in actively sensitized guinea-pig tracheas. The relaxing effect of epinephrine and vasoactive intestinal polypeptide (VIP) was tested in tracheal strips. Binding was studied with tracheal membranes and 125I-cyanopindolol. Antigen challenge resulted in a marked decrease of epinephrine-induced relaxation paralleled by a 50% reduction in beta-receptor number. The adrenergic system was specifically affected since VIP-induced relaxation was not modified by the anaphylactic reaction. In some experiments tissues were pretreated with hydrocortisone or indomethacin. Both these drugs prevented antigen exposure from impairing epinephrine relaxation, suggesting the involvement of eicosanoids in this phenomenon. Our data clearly indicate the occurrence of beta-receptor desensitization as a consequence of the anaphylactic reaction, thus impairment of the adrenergic system might play a role in asthma.

Animals↗
PubMed1989

In vivo modulation of striatal phosphoproteins by dopaminergic agents.

Protein phosphorylation in the brain represents a common target for several second messenger systems. A phosphoprotein (DARPP-32) specifically regulated by cAMP and dopamine has been detected in neurons bearing dopamine D-1 receptors, where it plays a key role in eliciting cAMP-mediated intracellular responses. The endogenous phosphorylation of this cytosolic protein is markedly affected after in vivo acute treatment with the selective D-1 agonist, SKF 38393. The amount of the DARPP-32 dephospho-form measured by a back-phosphorylation assay was decreased by about 30% in agonist-treated animals. This effect was completely counteracted by the concomitant administration of the selective D-1 antagonist, SCH 23390, but not by a selective D-2 antagonist. This first demonstration of in vivo modulation of the phosphorylation state of DARPP-32 could, as a biochemical approach, represent a useful tool to gain further insight into the cascade of biochemical events elicited by specific dopaminergic drugs.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1989

Methylazoxymethanol-induced microencephaly: persistent increase of cortical somatostatin-like immunoreactivity.

Treatment of pregnant rats with methylazoxymethanol (MAM) at day 15 of gestation induces a marked microencephaly in the offspring, characterized by impaired formation of interneurons in the areas affected. We have measured somatostatin immunoreactivity in the cortex, striatum and hippocampus of the offspring of pregnant rats treated with graded doses of MAM. A long-lasting increase in the cortical levels of this peptide was found, suggesting that somatostatinergic interneurons might be selectively spared by administration of the cytotoxic agent at this gestational age.

Animals↗
PubMed1989

Denervation and hyperinnervation in the nervous system of diabetic animals: III. Functional alterations of G proteins in diabetic encephalopathy.

G protein-mediated effects on cAMP production were evaluated in the corpus striatum of diabetic rats 5 and 14 weeks after alloxan injection by measuring both D1-receptor-induced stimulation and D2-receptor-mediated inhibition of adenylate-cyclase activity. At 5 weeks of diabetes, no obvious alterations of G protein functions were detected. Both dopamine-stimulated adenylate cyclase and bromocriptine-induced inhibition of enzyme activity were indeed similar in control and diabetic animals. Fourteen weeks after alloxan injection, profound alterations were observed. Dopamine-stimulated cAMP production was markedly increased in diabetic rats, whereas bromocriptine ability to reduce cAMP formation was almost abolished at this late stage of diabetes. Hypoactivity of Gi/Go proteins was also confirmed by the reduced ability of the GTP non-hydrolyzable analog GTP-gamma-S to inhibit forskolin-stimulation of adenylate cyclase. These results show an apparent functional imbalance between Gs and Gi/Go-mediated transduction mechanisms, with an increased efficacy of Gs activity likely due to the loss of Gi/Go inhibitory functions. Concomitantly with such transductional alteration detected in chronic diabetes, we observed a marked increase of the striatal content of met-enkephalin, which is known to utilize Gi/Go proteins for inhibition of adenylate cyclase. The measurement of other transmitters (vaso-active intestinal peptide, substance P, serotonin, noradrenaline, and dopamine) did not reveal any difference with respect to controls. The observed transductional defect in diabetic animals and the increased content and/or hyperinnervation by the metenkephalinergic system could be correlated as mutual compensatory mechanisms.

Adenylyl Cyclases↗
PubMed1989

Synthesis and dopamine receptor affinities of 6-amino-5,6,7,8-tetrahydroquinoline derivatives.

Some N,N-dialkylderivatives of 6-amino-5,6,7,8-tetrahydroquinoline were synthesized. The affinity of new compounds for dopamine binding sites was measured in a test involving displacement of [3H]SCH 23390 (D-1 selective) and [3H]spiperone (D-2 selective) from homogenized rat striatal tissue. While no compound was effective in displacing [3H]SCH 23390, in the binding assays on the D-2 receptor all tetrahydroquinolines displaced [3H]spiperone from specific binding sites, the compounds with a N-n-propyl-N-phenylethylamino group (18) or N,N-di n-propylamino group (16) being the most potent.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1989

Beta-adrenoceptor desensitization in a model of experimental asthma in guinea-pigs.

We investigated the possible occurrence of the desensitization of pulmonary beta-receptors in a model of experimental asthma such as the ovalbumin sensitized guinea-pig. Although some differences were observed between normal and asthmatic guinea-pigs, the desensitization procedure (isoproterenol (ISO) 10(-6) M x 20 min x 2) markedly impaired the relaxing capacity of ISO, epinephrine (EPI) and procaterol. With the beta 2 agonist procaterol, the sensitized tissues seemed to be more sensitive compared to normal. In parallel, the desensitization procedure produced a greater decrease in the relaxing capacity of procaterol in the sensitized tracheas. On the other hand, the two unselective beta-agonists (ISO and EPI) did not seem to discriminate between the two experimental conditions used. These data suggest that the immunological disturbance due to the active sensitization may induce a modification in beta-adrenoceptor reactivity. The results obtained with EPI after anaphylactic challenge are in agreement with this. In fact, the relaxing capacity of EPI was markedly reduced by antigen challenge.

Adrenergic beta-Agonists↗
PubMed1987

Adenosine modulates the dopaminergic function in the nigro-striatal system by interacting with striatal dopamine dependent adenylate cyclase.

Behavioral and pharmacological evidences suggest that dopaminergic mechanisms in striatum might be counteracted by adenosine or potentiated by its pharmacological antagonists methylxanthines. To test whether adenosine modulation of the dopaminergic function could be, at least in part, due to an interaction at the level of the adenylate cyclase complex, we studied the effects of the adenosine analog R-Phenyl-isopropil-adenosine (R-PIA) on basal and dopamine-sensitive adenylate cyclase in rat striatum. R-PIA, which interacts with both adenosine A1-inhibitory and A2-stimulatory receptors, dose-dependently inhibited the stimulation induced by dopamine, and seemed to utilize the same pool of enzyme linked to dopaminergic D1 receptors. Two experimental approaches leading to supersensitivity of striatal dopaminergic receptors, (i.e., 6-hydroxy-dopamine injection in substantia nigra and reserpine administration) also induced upregulation of adenosine-dependent adenylate cyclase in striatum, and altered R-PIA modulation of dopamine-sensitive adenylate cyclase. Conversely, after subchronic treatment with neuroleptics such as haloperidol or sulpiride, upregulation of 3H-Spiroperidol binding in striatum was not associated with changes of R-PIA dependent adenylate cyclase in this area. It is concluded that adenosine might modulate post-synaptic responses to dopamine via adenosine receptors which functionally interact with dopaminergic D1 receptors in striatum.

Adenosine↗
PubMedDate not supplied

Levels of NGF, p75NGFR and ChAT immunoreactivity in brain of adult and aged microencephalic rats.

Methylazoxymethanol (MAM)-induced microencephalic aged animals with reduced cortical mass and unmodified basal nucleus were used to study the relationship between cells that produce and cells that utilize NGF. Total cortical ChAT activity of MAM 2, 19 and 27 month old animals was reduced compared to their age-matched controls. To verify whether the reduction of enzyme activity can be ascribed to changes in or ablation of projecting neurons, we carried out immunohistochemical analysis of ChAT and low affinity NGF receptor (p75NGFR) in the basal nucleus of control and MAM-treated animals. ChAT and p75NGFR immunostaining of basal forebrain cholinergic neurons showed morphological changes in MAM animals, as revealed by cellular atrophy, reduced dendritic arborization and decreased staining intensity. In the cerebral cortex of microencephalic animals, reduced levels of NGF compared to controls were observed at all examined ages. These results suggest that MAM treatment induces long-lasting ablation of cortical NGF-synthesizing cells leading to reduced trophic support to basal forebrain cholinergic neurons, which might be responsible for the cellular atrophy observed in the basal nucleus.

Aging↗
PubMedDate not supplied

Peripheral blood abnormalities in Alzheimer disease: evidence for early endothelial dysfunction.

Clinical and epidemiologic studies demonstrate that vascular risk factors may be involved in Alzheimer disease (AD). To evaluate whether vascular abnormalities are an early feature of AD, several parameters of coagulation and fibrinolysis were assessed. Thirty patients with mild AD and 30 age-matched control subjects entered the study. All subjects performed a standardized clinical and laboratory protocol. Persons with vascular risk factors and systemic diseases were excluded. AD patients present significant increased levels of thrombomodulin (p < 0.0001) and sE-selectin (p < 0.03). In contrast, no difference was found between the two diagnostic groups in the levels of beta-thromboglobulin, prothrombin fragment 1+2, fibrinogen, and von Willebrand factor. No other association but diagnosis was found with thrombomodulin and sE-selectin. These findings suggest that endothelial dysfunction is an early event in AD patients.

Aged↗
PubMedDate not supplied

[Update of the Italian Society of Nephrology Project No. 1 of the 2004-2006 SIN programme].

In the last few years the Italian Society of Nephrology has addressed many technical-scientific and management aspects to better patient satisfaction. Project No. 1 of the 2004-2006 programme on 'Quality and Accreditation of National Renal Units' focuses on four essential points. The first is the questionnaire mailed to all the Presidents and Regional Delegates on the relationship between Nephrology units, Local Government Health-System and the Regional Healthcare Agency. The results evidence that the 'political' decision-making power of nephrologists decreases in the absence of a national strategy. The second point, in collaboration with the National Census Group, includes the quality analysis and the standardization of resources (human and structural) and management of the Renal Units. The third point is based on 'Educational Courses for Quality and Accreditation' held in Rome (3-5 October 2005: L'Accreditamento all'Eccellenza dell'Unita' Operativa di Nefrologia, Dialisi e Trapianto; 17-19 October 2005: Il Manuale di Accreditamento della Specialità di Nefrologia). The courses aim at training members responsible for each region to hold courses in their specific region to create a network including each single Renal Unit to create an acceptable homogenous language on the models of analysis and on the correct use of 'The Guide for Excellence Accreditation'. The fourth point concerns both the on-line Guide for Excellence Accreditation and 'Peer Review Accreditation' and the NEQUASY (Nephrology Quality System) project. The manual must be 'user friendly' allowing each Centre to self-evaluate using national and regional standards.

Accreditation↗