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Biomedical subjects

R M Di Giorgio

Publications and source records attributed to R M Di Giorgio.

At least 19 recordsLinked to original sources
PubMed1992

Polyamines are involved in retinoic acid-mediated induction of tissue transglutaminase in human peripheral blood monocytes.

The differentiation of human peripheral blood monocytes (HPBM) into macrophages, when cultured in vitro, has been associated with an increase in the expression of tissue transglutaminase (TGc). Retinoic acid (RA) addition to 5-day-old cultured monocytes, 36 h later induced about 5-folds increase of TGc content. The preliminary exposure of cultured monocytes to alpha-difluoromethylornithine (DFMO) significantly reduced TGc induction caused by RA. DFMO alone does not induce significant changes in the time-course of TGc activity. In cultured monocytes exposed to DFMO, putrescine and spermidine, but not spermine were significantly depleted. The supplementation of putrescine (1 mM) or spermidine (0.5 mM) to culture medium reversed the inhibiting effect of DFMO on RA-mediated induction of TGc. However, the addition of polyamines in the absence of RA or DFMO did not mimic the induction of TGc by RA. We conclude that TGc induction by RA during in vitro maturation of monocytes to macrophages may be modulated by polyamine availability.

Cell Differentiation↗
PubMed1988

Glucocorticoid regulation of spermidine acetylation in the rat brain.

The effect of glucocorticoids on polyamine metabolism has been elucidated further by measuring putrescine, spermidine, and spermine levels as well as ornithine decarboxylase, S-adenosylmethionine decarboxylase, and N1-acetylspermidine transferase activities in the hippocampus, cerebellar cortex, vermis, and deep nuclei of adrenalectomized rats. At 6 h after corticosterone or dexamethasone administration, the specific activities of ornithine decarboxylase and N1-acetylspermidine transferase showed the greatest increases in all brain tissues examined, and at 12 h, S-adenosylmethionine decarboxylase activity was not increased significantly. The hippocampus and cerebellar regions displayed different responses to corticosterone and dexamethasone, corresponding to the distribution of glucocorticoid and mineralocorticoid receptors. Corticosterone and dexamethasone increased ornithine decarboxylase and N1-acetylspermidine transferase activities in a dose-dependent manner, with dexamethasone being more active than corticosterone in all tissues. However, estradiol, progesterone, testosterone, and aldosterone were only active at doses greater than 5 mg/kg. The great increases in ornithine decarboxylase and N1-acetylspermidine transferase activities were accompanied by a marked increase in putrescine level and a small decrease in spermidine level. Our data confirm that the hippocampus and cerebellum are glucocorticoid target tissues and suggest that the increase in the content of putrescine, following acute treatment with glucocorticoids, is dependent on ornithine decarboxylase as well as N1-acetylspermidine transferase induction.

Acetylation↗
PubMed1985

Estrogen effects on nigral glutamic acid decarboxylase activity: a possible role for catecholestrogen.

Repeated but not single injections of estradiol benzoate significantly reduced nigral glutamic acid decarboxylase (GAD, EC 4.1.1.15). A single injection of the catecholestrogen 2-hydroxyestradiol produced similar results. Tolerance developed to the latter effect, as reflected by the lack of nigral GAD activity changes in rats repeatedly injected with 2-hydroxyestradiol. Repeated injection of the antiestrogen tamoxifen not only failed to antagonize the action of estradiol benzoate but itself reduced nigral GAD activity. Hypophysectomy, which itself decreased nigral GAD activity prevented the lowering effects of either repeated estradiol benzoate administration or single 2-hydroxyestradiol injection on the enzymatic activity.

Animals↗
PubMed1985

gamma-Aminobutyric acid metabolism and behavioral effects after intraventricular injection of spermine in chicks.

Effects of intraventricularly injected spermine on behavior and electrocortical activity and gamma-aminobutyric acid (GABA) metabolism after a single dose of 1.13 mumol/animal were studied. Decrease in locomotor activity, sedation or sleep, and electrocortical synchronization that lasted approximately 2 h were observed. In addition spermine caused a significant increase in GABA content in diencephalon and brainstem, 30 min after administration. Concomitantly a significant increase of glutamate decarboxylase (GAD) activity was observed in cerebral hemispheres, diencephalon, and brainstem. Reduction in gamma-aminobutyrate: alpha-oxoglutarate amino-transferase (GABA-T) levels occurred in the diencephalon along with a significant increase of GABA-T in the brainstem. The present results demonstrate that spermine has the capacity to affect GABA metabolism and are in favor of the suggestion that endogenous polyamines may modulate GABAergic mechanisms.

4-Aminobutyrate Transaminase↗
PubMed1984

Altered time course of changes in the hippocampal concentration of excitatory and inhibitory amino acids during kainate-induced epilepsy.

The temporal sequence of electrophysiological and biochemical correlates of epilepsy induced by systemic injection of kainic acid (15 mg/kg i.p.) was investigated in male rats. A significant decrease in the hippocampal concentration of glutamate and aspartate was observed 20 min after the injection. These decreases preceded both electrographic and behavioral manifestations of epilepsy, thus suggesting a causal relationship between acidic amino acid changes and the genesis of kainate-induced hyperactivity. About 30-45 min after kainate injection, a decrease in glutamate, aspartate, glycine and taurine and no change in GABA concentration were observed. Bioelectrical activity, recorded in the regio inferior (CA3) of the hippocampus or in the fascia dentata revealed the presence of high frequency bursts separated by a long-lasting depression of discharge. About 55-75 min after the injection, the number of spikes in each burst increased and the duration and frequency of interictal pauses decreased. This stage was characterized by a decrease in glutamate and aspartate, restoration to normal of glutamine, glycine and taurine and a decrease in GABA.

Amino Acids↗
PubMed1984

Phenolic and tyrosyl ring deiodination in thyroxine from rat retina during postnatal development.

To elucidate tetraiodothyronine (T4) metabolism in developing rat retina 5-monodeiodinating and 5'-monodeiodinating activities were studied. T4 was incubated with aliquots of homogenate or crude primary subcellular fractions, and the 3,3',5'-triiodothyronine (rT3) or 3,5,3'-triiodothyronine (T3) produced were measured by radioimmunoassay. Reaction rates were dependent on incubation time, tissue amount, temperature and pH. The optimum pH values were 7.8 and 7.2 respectively for rT3-forming and T3-forming systems. Conversion of T4 to either T3 or rT3 was dependent on dithiothreitol concentration, and the T4-5'-deiodinating activity was inhibited by propylthiouracil. Deiodinase activities were mainly found in the crude microsomes. The retinal 5'-monodeiodination rate of T4 was immeasurably low by the 2nd day and the highest values were reached on 15th day of postnatal development. On the other hand deiodination of the T4 tyrosyl ring shows a progressive decline from birth, and adult values were reached on the 15th day. Data support the hypothesis that, in developing rat thyroxine, phenolic and tyrosyl-ring deiodinase activities are present in the retina and their reciprocal changes may regulate morphological and biochemical cell maturation.

Animals↗
PubMed1984

Retina maturation following administration of thyroxine in developing rats: effects on polyamine metabolism and glutamate decarboxylase.

The effects of subcutaneous daily treatment with thyroxine on cell proliferation, differentiation, polyamines, and gamma-aminobutyric acid metabolism in the rat retina were studied during the first 20 postnatal days. The retinal layers of the treated rats displayed an enhanced cell differentiation which reached its maximum 9-12 days from birth; but this effect stopped very quickly and was finished by the 20th postnatal day. Primarily there was an increase in ornithine decarboxylase activity which was accompanied by an increase in putrescine, spermidine, and spermine levels. S-Adenosylmethionine decarboxylase was induced later than ODC; corresponding with the enhanced synaptogenesis, glutamate decarboxylase increased 15-fold between the fourth and 15th days. Our data are consistent with the hypothesis that thyroxine may exert some of its effects by inducing the enzymes which regulate polyamine metabolism and synaptogenesis.

Adenosylmethionine Decarboxylase↗
PubMed1984

Increased cardiovascular responsiveness to GABAergic stimulation in DOCA-salt hypertensive rats.

Cerebral glutamate decarboxylase (GAD) activity in DOCA-salt hypertensive rats showed a significant increase in the mesencephalon and a significant decrease in the cerebral cortex and in the cerebellum, compared to that observed in mononephrectomized normotensive animals. Intracerebroventricular (icv) injection of muscimol (0.5, 1 and 2 micrograms), a GABA receptor agonist, produced a dose-dependent decrease in heart rate (HR), significantly greater in freely moving hypertensive animals than in normotensive controls. Muscimol also reduced mean arterial pressure (MAP). The hypotensive effect induced by muscimol (2 micrograms) was significantly higher in hypertensive animals. Ethanolamine-O-sulphate (5, 10, 20 and 40 microM), an inhibitor of GABA breakdown, determined a decrease in MAP and in HR greater in hypertensive than in normotensive rats. Intraperitoneal injection of valproic acid (50-100 mg/Kg/die) for 6 weeks significantly reduced the development of DOCA-salt hypertension in rats. The anti-hypertensive effect became significant during the 4th week and was dose-dependent. DOCA-salt animals, daily treated with 50 mg/Kg of valproic acid, showed an increased pressor response to intravenous injection of phenylephrine (0.1, 0.5 and 1 microgram/Kg). Data strongly support an impairment of cerebral GABA control of blood pressure and heart rate in DOCA-salt hypertensive rats.

4-Aminobutyrate Transaminase↗
PubMed1983

Effects of thyroxine on methionine adenosyltransferase activity in rat cerebral cortex and cerebellum during postnatal development.

Methionine adenosyltransferase (MAT) activity was evaluated in cerebral cortex and cerebellum in controls and in rats treated with thyroxine. In controls the enzyme showed a different pattern in cerebral cortex and cerebellum during neonatal and late suckling periods. Hyperthyroid rats showed a significant increase of the enzyme in cerebral cortex only at the 2nd day of the neonatal period; in cerebellum the developmental pattern of MAT in neonatal period was anticipated temporally by 2-4 days. During the late suckling period thyroxine treatment produced in cerebellum a significant decrease in MAT activity at the 15th day after birth. From these data, we propose that hyperthyroidism may cause precocious induction of MAT both in cerebral cortex and in cerebellum and that the increased availability of S-adenosyl-L-methionine during the neonatal period could be related to its utilization also in polyamine biosynthesis.

Animals↗
PubMed1983

Effects of hyper- and hypoprolactinemia on glutamate decarboxylase activity in medial basal hypothalamus of male rat.

Haloperidol, sulpiride, domperidone and apomorphine, drugs which influence dopamine (DA) receptors and in turn prolactin (PRL) secretion have been shown to induce parallel changes in medial basal hypothalamic (MBH) glutamate decarboxylase (GAD) activity and serum PRL levels. The possibility that PRL may be involved in the effects of the drugs on MBH GAD activity is suggested in view of the evidence that hypophysectomy completely prevents drug-induced MBH GAD activity changes and that hyperprolactinemia by anterior pituitary homograft results in a significant, although small, change in the enzymatic activity.

Animals↗
PubMed1982

Effects of calcitonin on rat extrapyramidal motor system: behavioral and biochemical data.

The effects of i.v.c. injection of human and salmon calcitonin on biochemical and behavioral parameters related to the extrapyramidal motor system, were investigated in male rats. Calcitonin injection resulted in a potentiation of haloperidol-induced catalepsy and a partial prevention of apomorphine-induced hyperactivity. Moreover calcitonin induced a significant decrease in nigral GAD activity but no change in striatal DA and DOPAC concentration or GAD activity. The results are discussed in view of a primary action of calcitonin on the striatonigral GABAergic pathway mediating the DA-related behavioral messages of striatal origin.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1982

Sulpiride effects on nigral and striatal glutamic acid decarboxylase activity: a possible involvement of prolactin.

Sulpiride, a benzamide derivative neuroleptic, was shown to significantly increase glutamic acid decarboxylase activity in substantia nigra and corpus striatum in either acutely or chronically injected male rats. Hypophysectomy completely prevented this effect suggesting an involvement of an anterior pituitary factor in the central action of sulpiride. Prolactin might possibly mediate the effects of sulpiride since it is known to increase prolactin secretion by an action at the level of the anterior pituitary. Consistent with this hypothesis was the finding of a similar increase in nigral and striatal glutamic acid decarboxylase activity in hyperprolactinemic animals in which an anterior pituitary had been implanted under the kidney capsule.

Animals↗
PubMed1982

S-adenosylmethionine decarboxylase levels in rat retina during postnatal development.

S-Adenosylmethionine decarboxylase from rat retina is similar to that isolated from other rat tissues with regard to kinetic parameters, pH optimum, putrescine requirement, and sensitivity to spermine. The enzymic activity increases during the first 7 days of postnatal life but decreases until the 20th day. After this period AdoMet decarboxylase activity increases, to reach the highest values at the 90th day. This behavior suggests that such enzymic activity is responsible for spermidine and spermine levels in rat retina and that a high content of retinal spermine might have a role in the photoreceptor outer segment renewal.

Adenosylmethionine Decarboxylase↗
PubMed1981

[Effects of different doses of apomorphine on the glutamate decarboxylase activity of the substantia nigra and the medial basal hypothalamus].

The activity of gamma-aminobutyric acid (GABA) synthesizing enzyme glutamic acid decarboxylase (GAD, EC 4.1.1.15) was assayed in the rat substantia nigra (SN) and medial basal hypothalamus (MBH) following systemic injection of different doses of the dopamine receptor agonist apomorphine. In SN, the highest dose of apomorphine (1000 micrograms/kg) causes an increase of the GAD activity whilst an opposite effect is observed with the lowest dose (35 micrograms/kg). Results obtained in SN are in accordance with previous neurochemical and behavioural data suggesting an opposite action of high (500 micrograms/kg) and low doses (100 micrograms/kg) of apomorphine in nigro-striatal system, probably due to the existence of two classes of dopamine receptors, i.e. classical postsynaptic dopamine receptors and presynaptic inhibitory dopamine autoreceptors. In MBH, the evidence for similar effects of low and high doses of apomorphine (the decrease of GAD activity) may suggest that, as already reported, at this level only one class of dopamine receptors is present.

Animals↗
PubMed1981

Effects of chronic haloperidol and sulpiride treatment on rat nigral GABA content.

The effects of chronic haloperidol and sulpiride treatment on nigral GABA content were investigated in rats. Chronic sulpiride treatment is capable of inducing an increase in nigral GABA content whilst no significant effect is observed following chronic haloperidol treatment at the doses used. The different effects of haloperidol and sulpiride on nigral GABA content were related to the different neuropharmacological spectrum of the two drugs.

Animals↗
PubMed1981

Effects of different doses of apomorphine on GAD activity in rat substantia nigra.

The effects of different doses of the dopamine (DA) receptor agonist apomorphine on the activity of the gamma-aminobutyric acid (GABA)-synthesizing enzyme glutamic acid decarboxylase (GAD, EC 4.1.1.15) were investigated in rat substantia nigra in comparison with haloperidol and sulpiride, two DA receptor blocking agents. Results obtained show that low doses (10,35 microgram/kg, s.c.) of apomorphine induce a decrease in nigral GAD activity whilst an opposite effect is observed with the highest dose (1000 microgram/kg, s.c.). No significant change is observed following injection of the intermediate doses (100 and 500 microgram/kg, s.c.). Moreover, sulpiride at the dose used (2 mg/kg, i.p.) induces an increase in GAD activity whilst no effect follows systemic injection of the same dose of haloperidol. The results are discussed in light of recent neurochemical and behavioral data.

Animals↗