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M Baraldi

Publications and source records attributed to M Baraldi.

At least 73 records · Page 4Linked to original sources
PubMed1985

Opiate receptors and beta-endorphin levels in brain areas of dogs with portal-systemic encephalopathy.

Clinical observation has indicated a supersensitivity to morphine in patients with hepatic encephalopathy. With the aim of clarifying the issue, radioreceptor binding studies of opiate receptors were performed in frontal cortex and hypothalamus of 6 dogs with mild portal-systemic encephalopathy induced by chronic treatment with dimethylnitrosamine followed by porto-caval shunt end-to-side. beta-Endorphin assays were performed in the same areas with radioimmunoassay. Opiate receptors labeled with [3H]naloxone in both areas showed a significant increase in the receptor densities (Bmax) without changes in the dissociation constant (KD). In parallel beta-endorphin levels showed a decline during the development of encephalopathy in both areas. The increased densities of opiate receptors in the mild stage of encephalopathy may explain the supersensitivity to morphine in patients with liver diseases.

Animals↗
PubMed1985

Opioid peptides of the pituitary and hypothalamus: changes in pregnant and lactating rats.

Immunoreactive (Ir) beta-endorphin concentrations were determined in plasma, anterior pituitary (AP), neurointermediate pituitary lobe (NIL) and mediobasal hypothalamus (MBH) of pregnant (12-14 and 18-20 days) and fertile control rats, during labour and lactation. Immunoreactive Met-enkephalin concentrations were also evaluated in the MBH. Concentrations of Ir beta-endorphin in plasma, AP and NIL of rats during early and late pregnancy were significantly higher than in controls, the plasma and AP contents showing an increasing pattern in the second half of gestation. During labour, Ir beta-endorphin concentrations in plasma and AP reached the highest values, whereas those in NIl remained unchanged. Lactating rats showed Ir beta-endorphin concentrations in NIL and plasma in a range similar to that found in pregnant rats, resulting in concentrations in the AP not significantly different from those of nonpregnant controls. Immunoreactive beta-endorphin and Ir Met-enkephalin concentrations in MBH of pregnant rats were almost twice as high as in controls, rising markedly during labour; during lactation levels were in the same range as in non-pregnant controls. These results indicate that pregnancy and labour are characterized by high plasma, pituitary and hypothalamic concentrations of Ir-beta-endorphin as well as by high hypothalamic Ir Met-enkephalin levels, and that Ir beta-endorphin concentrations vary differently during pregnancy, lactation and labour in the two pituitary lobes, supporting the existence of different control mechanisms in the AP and NIL.

Animals↗
PubMed1984

Dopamine receptors in the guinea-pig heart. A binding study.

The binding of dopaminergic agonists and antagonists to guinea-pig myocardial membrane preparations was studied using 3H-dopamine and 3H-spiperone as radioligand. 3H-Dopamine bound specifically to heart membranes while 3H-spiperone did not. A Scatchard analysis of 3H-dopamine binding showed a curvilinear plot indicating the presence of two dopamine receptor populations that we have termed high- (Kd = 1.2 nM, Bmx = 52.9 fmol/mg prot.) and low- (Kd = 11.8 nM, Bmx = 267.3 fmol/mg prot.) affinity binding sites, respectively. The characterisation of the high-affinity component of 3H-dopamine binding indicated that the binding is rapid, saturable, stereospecific, pH- and temperature-dependent, and displaced by dopaminergic agonists and antagonists known to act similarly in vivo. The finding that pretreatment with dibenamine (which has been described as an alpha-adrenoceptor irreversible blocker) did not affect the binding of dopamine to cardiac membrane preparations suggests that alpha-adrenoceptors and dopamine receptors have separate recognition sites in the heart. We conclude that 3H-dopamine binds to specific dopamine receptors in the heart of guinea-pigs.

Animals↗
PubMed1984

Toxins in hepatic encephalopathy: the role of the synergistic effect of ammonia, mercaptans and short chain fatty acids.

Evidence has been recently produced that neurological changes which characterize hepatic encephalopathy due to fulminant hepatic failure in rats are linked with a pathology of GABA receptors. In the search for the peripheral toxins responsible for the CNS impairment present in hepatic encephalopathy it has been shown that the administration of ammonia and mercaptans and octanoic acid in normal rats reproduced behavioural and electrophysiological changes similar to those seen in galactosamine induced encephalopathy. The present report shows that a subacute administration of the above toxins induced a marked alteration of the GABA receptor complex which may account for the CNS derangement of hepatic encephalopathy.

Ammonia↗
PubMed1984

Supersensitivity of benzodiazepine receptors in hepatic encephalopathy due to fulminant hepatic failure in the rat: reversal by a benzodiazepine antagonist.

Benzodiazepine receptors were studied in rats with hepatic encephalopathy due to fulminant hepatic failure induced by galactosamine. [3H]-Diazepam binding studies on brain synaptic membranes of rats with mild and severe encephalopathy show a significant increase in the number of receptors in both stages of coma. [3H]Diazepam binding to synaptic membrane preparations from rats in the mild or severe stage of encephalopathy hyper-responded to the stimulatory effect of gamma-aminobutyric acid (GABA) applied in vitro at doses which for control rat preparations were in a subthreshold range. The effect of GABA was shown to be specific, since it was blocked by bicuculline methiodide. The sensitivity of benzodiazepine receptors in hepatic encephalopathy to nanomolar concentrations of GABA, which induced a significant increase in their affinity, seems to indicate a functional supersensitivity of benzodiazepine receptors in vivo in both mild and severe stages of encephalopathy. The phenomena described may be attributed to a partial degeneration of nerve terminals in hepatic encephalopathy, leading to a supersensitivity of benzodiazepine receptors, which parallels the previously described denervation supersensitivity of GABA receptors present in this animal model of fulminant hepatic failure. These findings may account for the brain hypersensitivity to sedatives administered to patients with liver diseases. The administration in vivo of a benzodiazepine antagonist, 2-phenylpyrazolo[4,3-c]-quinolin-3(5H)-one, counteracted the hypersensitivity of benzodiazepine receptors in the mild stage of encephalopathy.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1983

Down regulation of striatal dopamine receptors in experimental hepatic encephalopathy.

Dopamine receptors were studied in striatal synaptosomes prepared from rat brain with hepatic encephalopathy induced by galactosamine-HCl and documented by visual evoked potential recordings. In order to further characterize the model, plasma amino acid levels and striatal catecholamines and octopamine levels were assayed. In agreement with previous reports in animal and in man, plasma amino acids were increased both in mild and severe stage of this pathology. Striatal levels of norepinephrine and dopamine fell during the development of coma while octopamine rose. Dopamine binding studies showed a decrease in the affinity during the mild stage and a reduction of receptor numbers in the severe stage of encephalopathy. The overall results, in the light of previous reports on GABA receptor studies, seem to indicate the presence in the development of encephalopathy of an imbalance between the dopaminergic and the GABAergic system leading to a prevalence of GABAergic inhibitory system.

Amino Acids↗
PubMed1983

Antidepressants and opiates interactions: pharmacological and biochemical evidences.

Imipramine, chronically administered to rats (20 mg/Kg/day X 20) has a potent analgesic effect per se (hot plate test), increases morphine analgesia and intensifies morphine withdrawal syndrome precipitated by naloxone. Receptor binding studies performed with 3H-naloxone revealed that chronic administration of imipramine results in a marked increase of opiate binding sites in the brain. This increase persisted when the rats treated chronically with imipramine were rendered tolerant to morphine by s.c. implantation for 3 days of a pellet containing 100 mg of morphine. Since antidepressants exert their own analgesic effect, increase morphine analgesia and displace opiate receptor binding, it may be that by interacting with the opiate receptor complex imipramine induces supersensitivity in opiate recognition binding sites.

Analgesics↗
PubMed1982

Experimental hepatic encephalopathy: changes in the binding of gamma-aminobutyric acid.

Two populations of receptors for gamma-aminobutyric acid, one with low- and the other with high-affinity characteristics, are detectable in frozen, thawed, Triton-treated synaptic membrane preparations from normal brain. It is now reported that membrane preparations from rats with mild galactosamine-induced hepatic encephalopathy show an increase in the number of low- and high-affinity gamma-aminobutyric acid binding sites, whereas those from rats with severe encephalopathy show only high-affinity binding sites. Thus, hepatic encephalopathy appears to involve partial degeneration of the gamma-aminobutyric acid-containing presynaptic nerve terminals.

Bicuculline↗
PubMed1982

Metabolism and brain uptake of gamma-aminobutyric acid in galactosamine-induced hepatic encephalopathy in rats.

Kinetic studies of [3H]gamma-aminobutyric acid ([3H]GABA) after an intravenous injection were performed in normal rats and in rats with severe degree of hepatic encephalopathy due to fulminant hepatic failure induced by galactosamine. Moreover, plasma and brain GABA levels, and GABA and glutamic acid decarboxylase activity were studied in some brain areas. After intravenous injection, [3H]GABA disappeared very rapidly in the blood of normal rats, with a prompt increase of 3H metabolites. In comatose rats, a delayed disappearance of [3H]GABA was parallelled by a lower amount of metabolites, indirectly indicating a peripheral decrease of GABA-transaminase activity. The amount of [3H]GABA in brain was lightly but constantly lower in comatose rats than in controls, indicating that the change in permeability of the blood-brain barrier in hepatic encephalopathy does not affect the [3H]GABA uptake of the brain. Furthermore, the assay of endogenous GABA in blood, whole brain, and brain areas did not show any significant difference in any of the two groups. The finding that glutamic acid decarboxylase activity in brain was reduced, together with the indirect evidence of a reduction in GABA-transaminase, may account for the steady state of GABA in hepatic encephalopathy. However, the reduction in glutamic acid decarboxylase activity is in favor of a functional derangement at the GABA-ergic nerve terminals in this pathological condition.

Animals↗
PubMed1979

GABA receptors in clonal cell lines: a model for study of benzodiazepine action at molecular level.

A "recptor unit" for gamma-aminobutyric acid (GABA), which includes brainlike receptor binding sites for tritium-labeled GABA and benzodiazepines (diazepam, clonazepam, and flunitrazepam) and a thermostable endogenous protein (GABA modulin) that inhibits both GABA and benzodiazepine binding, has been demonstrated in membranes prepared from NB2a neuroblastoma and C6 glioma clonal cell lines. In these cells, as in brain, diazepam (1 micromolar) prevents the effect of GABA modulin, and in turn GABA (0.oma and, to a lesser extent, the glioma cells represent a suitable model to study the interactions and the sequence of membrane and intracellular events triggered by the stimulation of benzodiazepine and GABA receptors.

Animals↗
PubMed1979

Molecular mechanisms regulating the interactions between the benzodazepines and GABA receptors in the central nervous system.

Using radioreceptor assay techniques to measure the kinetics of GABA and diazepam receptors, a relationship between GABA and benzodiazepine receptors has been firmly established in membranes of brain and neuroblastoma NB2a clonal cell lines. Occupancy of benzodiazepine receptors uncovers a new population of GABA receptors (GABA2 receptors) endowed with high affinity for GABA. Moreover, stimulation of GABA receptors increases the affinity of 1,4-benzodiazepine receptors for 1,4-benzodiazepines. This reciprocal interaction appears to be mediated by an endogenous regulatory protein (for details on this protein see [14 and 29]) which allosterically regulates GABA2 receptors while it competitively interacts with benzodiazepines for their specific binding sites. The rank order of potency of the various 1,4-benzodiazepines to block the action of this protein inhibitor on GABA receptors is related to their capacity to displace 3H-diazepam binding. These data suggest that the interaction between the 1,4-benzodiazepine receptors and the endogenous protein modulator of GABA2 receptors might play a role in the pharmacological action of the 1,4-benzodiazepines.

Animals↗
PubMed1979

1,4-Benzodiazepines and gamma-aminobutyric acid: pharmacological and biochemical correlates.

The high affinity receptors or GABA present in brain interact with an endogenous thermostable inhibitor (GABA modulin) which allosterically modifies GABA binding sites. This is the type of GABA receptor that we term GABA2 receptor in comparison to GABA1 receptor which has low affinity for GABA and is not regulated by GABA modulin. The 1,4-benzodiazepines interact competitively with GABA modulin and thereby modify GABA2 receptor binding. In contrast the occupancy of GABA receptor increases the affinity of 1,4-benzodiazepine receptors for their specific agonist. The GABA modulin and both GABA receptors are located on the membranes of C6 and NB2a cells. The NB2a cell membranes also contain CL- ionophore, thus the complete receptor complex is present in the membranes of NB2a cell clone. It was proposed that the inability of clonazepam to displace 3H-diazepam from specific binding sites characterizes the nonneuronal 1,4-benzodiazepine receptor. This characterization was shown to relate to the properties of other membrane components rather than to the characteristics of the specific benzodiazepine receptors.

Animals↗