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M L Barbaccia

Publications and source records attributed to M L Barbaccia.

At least 37 records · Page 2Linked to original sources
PubMed1992

Cyclic AMP-dependent increase of steroidogenesis in brain cortical minces.

Rat brain cortical minces were incubated with forskolin and dibutyryl-cyclic AMP for 60 and 30 min, respectively. The concentrations of pregnenolone, progesterone and desoxycorticosterone in this preparation were significantly increased by both substances. The results indicate that, in brain tissue, steroidogenesis appears to be regulated by receptor transduction mechanisms that operate through adenylate cyclase.

Animals↗
PubMed1990

DBI (diazepam binding inhibitor): the precursor of a family of endogenous modulators of GABAA receptor function. History, perspectives, and clinical implications.

Biochemical, electrophysiological, and lately, molecular biological techniques have shown that GABAA receptors are heterogeneous supramolecular complexes and can be divided into at least three major subgroups: GABAA1, GABAA2, and GABAA3. They differ mainly in the structural and functional properties of the allosteric modulatory center associated with each one of them. This paper will review the present state of research based on the evidence that DBI (diazepam binding inhibitor) and its natural processing products can selectively modulate GABAergic transmission at different GABAA receptor subtypes. Furthermore, the possibility that the DBI family of peptides represents a novel and meaningful neurochemical correlate for neuropsychiatric pathology, sustained by an alteration of GABAergic transmission, will be discussed.

Animals↗
PubMed1989

Cerebrospinal fluid content of diazepam binding inhibitor in chronic hepatic encephalopathy.

The neuropeptide diazepam binding inhibitor (DBI) is an endogeneous allosteric modulator of gamma-aminobutyric acid (GABA) receptors at the benzodiazepine recognition site. Recent theories on the neurochemical cause for hepatic encephalopathy have implicated activation of inhibitory neurotransmitter GABA systems. In 20 patients with hepatic disease, blood and cerebrospinal fluid (CSF) levels of ammonia and amino acids were measured. As in previous studies there was a selective elevation of CSF amino acids as well as a correlation between CSF glutamine levels and encephalopathy. CSF DBI levels were maximally elevated 5-fold in patients with hepatic encephalopathy, but they were normal in those patients with liver disease not associated with changes in mental status and in patients with nonhepatic encephalopathy. Levels of DBI correlated with the clinical staging of hepatic encephalopathy. These data suggest that DBI may participate in the modulation of cerebral function in hepatic encephalopathy.

Adult↗
PubMed1989

In primary cultures of cerebellar granule cells the activation of N-methyl-D-aspartate-sensitive glutamate receptors induces c-fos mRNA expression.

L-Glutamate, the natural agonist of quisqualate- and N-methyl-D-aspartate (NMDA)-sensitive excitatory amino acid receptors, elicits a rapid, transient, dose-dependent increase of the steady state level of c-fos mRNA followed by an accumulation of c-fos protein immunostaining in cell nuclei. This induction is prevented by 2-amino-5-phosphonovalerate, an isosteric glutamate receptor antagonist, and by Mg2+ ion and phencyclidine, two noncompetitive allosteric antagonists of NMDA-sensitive glutamate receptors. Kainate and quisqualate (up to 150 microM) failed to alter the basal expression of c-fos mRNA. Furthermore, glycine, a positive allosteric modulator of NMDA-sensitive glutamate receptors, potentiated the glutamate response in a strychnine-insensitive manner. Activation of other transmitter receptors present in these cells (gamma-aminobutyric acid(A), gamma-aminobutyric acid(B), and muscarinic) failed to increase c-fos mRNA expression. Our results provide evidence that activation of NMDA-sensitive glutamate receptors plays an exclusive role in the induction of c-fos mRNA expression and translation in primary cultures of granule cells. It can be inferred that, by this mechanism, glutamate can initiate a transcriptional program that may result in changes in the simultaneous expression of a set of target genes involved in neuron-specific responses.

Animals↗
PubMed1987

Activation of specific glutamate receptor subtypes increases C-fos proto-oncogene expression in primary cultures of neonatal rat cerebellar granule cells.

In primary cultures of rat cerebellar granule cells the activation of excitatory amino acid receptors by 1-glutamate enhances the steady state level of c-fos proto-oncogene messenger RNA. This effect is blocked by magnesium (1mM) as well as by the glutamate receptor antagonist 2-amino-5-phosphono-valerate (APV). Among the other excitatory amino acid agonists N-methyl-D-Aspartate (NMDA) and quisqualate also increased c-fos mRNA content, the latter however to a significantly lesser extent, while kainate failed to modify the basal level of c-fos expression. The addition of the muscarinic agonist carbachol or of the inhibitory neurotransmitter GABA did not affect the basal level of c-fos mRNA. This data demonstrate for the first time that activation of signal transduction at a specific excitatory amino acid receptor subtype can increase the steady state level of c-fos proto-oncogene mRNA in primary culture of cerebellar neurons.

Animals↗
PubMed1987

Effect of a protracted antidepressant treatment on signal transduction and [3H](-)-baclofen binding at GABAB receptors.

In membranes prepared from frontal cortex of rats receiving desmethylimipramine (10 mg/kg i.p. twice daily) or imipramine (7.5 mg/kg i.p. twice daily) for 3 weeks, the density of high-affinity gamma-aminobutyric acid (GABA)B recognition sites is increased when measured by [3H]GABA binding in the presence of an excess of bicuculline, but it is unchanged when measured by [3H](-)-baclofen binding. When the atypical antidepressant maprotiline was administered (10 mg/kg i.p. twice daily for 3 weeks), no change in the density of GABAB recognition sites was observed using either [3H]GABA or [3H](-)-baclofen as ligands. In addition, a protracted treatment with imipramine, desmethylimipramine and maprotiline failed to change GABAB receptor-coupled signal transduction as monitored by the ability of (-)-baclofen to inhibit the forskolin-stimulated adenylate cyclase activity in membranes prepared from frontal cortex and hippocampus or the cyclic AMP formation in slices from frontal cortex. Hence, after protracted antidepressant treatment, the increase of [3H]GABA binding may not reflect changes in the characteristics of the recognition sites of the GABAB receptors subclass coupled to the adenylate cyclase through a guanine nucleotide binding protein inhibitory (Ni).

Adenylyl Cyclases↗
PubMed1986

[3H]imipramine displacement and 5HT uptake inhibition by tryptoline derivatives: in rat brain 5-methoxytryptoline is not the autacoid for [3H]imipramine recognition sites.

A putative endacoid capable of displacing [3H]imipramine from its high affinity binding site and of inhibiting [3H]serotonin (5HT) uptake has been partially purified from rat brain tissue. It appears to be unevenly distributed in various rat brain structures following a pattern that only partially matches the extent of the serotonergic innervation in the rat brain structures investigated. The highest amounts have been recovered in striatum followed by hippocampus, cerebral cortex, brain stem and less in diencephalon, cerebellum, hypothalamus, olfactory bulb. Virtually no inhibitory activity on [3H]imipramine binding or on [3H]5HT uptake in addition to 5HT has been found in rat pineal extracts. Its absence in the pineal and various chemicophysical properties discussed in this report suggest that the rat brain endacoid for the imipramine binding site is not 5-methoxytryptoline, a compound previous proposed as the candidate for the role of endogenous ligand of [3H]imipramine recognition site. Moreover, the study of a series of tryptoline derivatives indirectly supports these conclusions.

Animals↗
PubMed1986

Diazepam-binding inhibitor. A brain neuropeptide present in human spinal fluid: studies in depression, schizophrenia, and Alzheimer's disease.

Diazepam-binding inhibitor is a novel peptide purified to homogeneity from rat and human brain. Diazepam-binding inhibitor is present, though not exclusively, in gamma-aminobutyric acid (GABA)-containing neurons where it is believed to inhibit GABAergic neurotransmission mediated by GABA by binding to the benzodiazepine-GABA receptor complex. Since an impairment of central GABAergic tone has been postulated to be associated with a number of neuropsychiatric disorders, we measured human diazepam-binding inhibitor immunoreactivity in the cerebrospinal fluid (CSF) of patients suffering from endogenous depression, schizophrenia, and dementia of the Alzheimer's type. Patients with major depression had significantly higher concentrations of human diazepam-binding inhibitor immunoreactivity in CSF when compared with age- and sex-matched normal volunteers, while no difference in CSF diazepam-binding inhibitor immunoreactivity was found in schizophrenics or patients with dementia of the Alzheimer's type when compared with controls. The possibility is discussed that the increased CSF human diazepam-binding inhibitor immunoreactivity observed in depressed patients may represent a functional disinhibition of GABAergic neurotransmission associated with depression.

Adult↗
PubMed1986

Abnormality of alpha 1-adrenergic receptors in the frontal cortex of epileptic rats.

We found that the binding of [3H]prazosin, a selective ligand for alpha 1-adrenergic recognition sites, is significantly lower in the frontal cortex of the genetically epilepsy-prone rats (GEPRs), as compared with normal Sprague-Dawley rats. Scatchard analysis reveals a decrease in the Bmax of [3H]prazosin binding with no change in the apparent KD, suggesting that there are fewer alpha 1-adrenergic recognition sites in the frontal cortex of the GEPR. This abnormality is associated with a reduced capacity of norepinephrine (NE) to stimulate [3H]inositol monophosphate ([3H]IP1) formation in frontal cortex slices prelabeled with [3H]inositol. No significant differences in [3H]prazosin binding as well as NE-stimulated [3H]IP1 formation have been observed in other brain regions including hippocampus, corpus striatum, and inferior colliculus. These results indicate that a deficit in the alpha 1-adrenergic receptor system in the frontal cortex may play a role in the seizure process in the GEPR.

Animals↗
PubMed1986

Maprotiline: an antidepressant with an unusual pharmacological profile.

Maprotiline, which differs from other typical tricyclic antidepressants for its tetracyclic structure, is a highly selective inhibitor of norepinephrine reuptake. Despite its in vitro and in vivo inhibitory activity on NE uptake, 21 repeated daily injections of maprotiline (20 mg/kg i.p.) neither attenuated the norepinephrine-stimulated cAMP accumulation nor reduced the number of beta adrenergic recognition sites in rat frontal cortex. Also, the number of brain serotonin2 recognition sites labeled by [3H]ketanserin remained virtually unchanged in rats receiving 21 daily injections of maprotiline. [3H]Desmethylimipramine and [3H]mianserin specific binding sites were also unmodified by repeated maprotiline injections. However, after 3 weeks of daily administrations, maprotiline elicited a significant decrease in the number of [3H]flunitrazepam binding sites and a decrease in the apparent affinity of [3H]beta-carboline ethylester binding to crude synaptic membranes prepared from hippocampal and hypothalamic homogenates. These changes appear to be unrelated to modifications in the concentration of endogenous gamma-aminobutyric acid present in the membrane preparation, since the addition of 100 microM bicuculline to the incubation mixture decreases [3H]flunitrazepam binding to the same extent in saline- and maprotiline-treated rats. It is suggested that repeated maprotiline injections may elicit an increase in the hypothalamic and hippocampal tissue levels of an endogenous substance(s) which binds to the benzodiazepine/beta-carboline recognition sites.

Animals↗
PubMed1985

Different effects of serotonin antagonists on 3H-mianserin and 3H-ketanserin recognition sites.

In minces prepared from the frontal cortex of rats treated with ketanserin (10 mg/kg i.p.) or mianserin (5 mg/kg i.p.) twice daily for 21 days, the Vmax of the adenylate cyclase stimulated by NE (100 microM) is attenuated, suggesting that ketanserin and mianserin share with a number of antidepressants the ability to attenuate the adenylate cyclase stimulation by NE. Ketanserin, given with the above mentioned dose schedule for 7 consecutive days, reduced the Bmax of 5HT2 recognition sites but failed to change either the Bmax or the apparent Kd of H-mianserin binding. A significant decrease in the Bmax of 5HT2 binding sites is elicited also by a single injection of mianserin (1). This drug also down-regulates its own binding when given twice daily for 3 weeks. From this and other information (2,3), it is concluded that ketanserin and mianserin bind to distinct recognition sites. The possibility that 5HT2 and mianserin recognition sites are functionally related and that serotonergic synapses are modulated by multiple chemical signals might be considered.

Animals↗
PubMed1984

The (-)-deprenyl actions on beta-adrenergic receptors require the integrity of brain serotonergic axon terminals.

In rats receiving (-)-deprenyl (1 mumol/kg, s.c.) twice daily for 3 weeks, the Bmax of imipramine binding sites located in crude synaptic membranes prepared from frontal cortex increases while the NE stimulation of cAMP accumulation in minces prepared from frontal cortex is attenuated. The presence of intact 5HT axon terminals is an absolute requirement for the down-regulation of the beta-adrenergic receptor function by repeated injections of (-)-deprenyl. These and other lines of evidence suggest that the increase in the Bmax of [3H]imipramine binding sites and the attenuation of beta-adrenergic receptor function elicited by (-)-deprenyl might be causally related.

5,7-Dihydroxytryptamine↗
PubMed1984

Comparison of iprindole, imipramine and mianserin action on brain serotonergic and beta adrenergic receptors.

Iprindole in vitro displaces mianserin from specific recognition sites (IC50 3 microM). Daily doses (5 mg/kg i.p.) of iprindole repeated for 3 weeks attenuate the norepinephrine stimulation of adenylate cyclase studied in brain slices. Whereas the attenuation of noradrenergic receptor function elicited by imipramine can be antagonized by lesions of serotonergic axons, the inhibition of norepinephrine-induced stimulation of adenylate cyclase elicited by iprindole or mianserin is not inhibited by serotonin axon lesions. Iprindole given daily repeatedly reduces the maximal number of binding sites of [3H]mianserin and [3H]ketanserin; both actions are unchanged by lesions of central serotonergic axons.

Animals↗