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S Consolo

Publications and source records attributed to S Consolo.

At least 19 recordsLinked to original sources
PubMed1992

Mechanism of the galanin induced increase in acetylcholine release in vivo from striata of freely moving rats.

Galanin (GAL) administered intracerebroventricularly (i.c.v.) induced a strong and long-lasting increase in the basal acetylcholine (ACh) release from striata of freely moving rats only when the excitatory corticostriatal input was removed, while its effect was transient in striata of sham-operated rats. This effect was dose-dependent (0.78, 1.56 and 3.12 nmol) and was completely prevented by the GAL receptor antagonist, galantide. GAL injected locally (3.12 nmol) in deafferented striata also induced a persistent increase in ACh release although to a lower extent. The impairment of monoaminergic neurotransmission caused by alpha-methylparatyrosine or p-chlorophenylalanine, respectively inhibitors of catecholamine and serotonin synthesis, completely prevented the rise in ACh output from deafferented striata while the muscarinic antagonist, scopolamine (0.5 mg/kg, s.c.), failed to do it. The data suggest that GAL in the deafferented striatum facilitates basal ACh release through an indirect mechanism. The effect seems to be at least partly mediated by an action of GAL on specific receptors in the striata.

Acetylcholine↗
PubMed1992

Galanin reduces PDBu-induced protein phosphorylation in rat ventral hippocampus.

The effect of galanin (GAL) on basal and phorbol-12,13-dibutyrate (PDBu) induced protein phosphorylation in rat ventral hippocampal miniprisms was investigated. GAL (0.5, 1 and 2 microM) inhibited PDBu stimulation in a concentration-dependent manner without altering basal protein phosphorylation. This inhibitory effect was prevented by the GAL antagonist galantide. GAL did not affect either the activity of protein kinase C (PKC) from rat brain or basal phosphorylation in ventral hippocampal hippogenates, suggesting that it did not directly modulate PKC activity. Depolarization of miniprisms from ventral hippocampi by 18 mM K+ prevented the effect of GAL on PDBu-induced phosphorylation. The results indicate that GAL indirectly regulates neuronal protein phosphorylation by a GAL receptor-mediated action.

Animals↗
PubMed1992

Effect of tianeptine on the central cholinergic system: involvement of serotonin.

The effect of tianeptine on in vivo acetylcholine (ACh) release from brain hemispheric regions of freely moving rats was investigated using the microdialysis technique coupled with a sensitive radioenzymatic method. Tianeptine, at the dose of 30 mg/kg i.p., reduced ACh release from dorsal hippocampi by 40% in 40 min, and induced a 30% decrease of ACh output from frontal cortices while at the doses of 10 and 20 mg/kg it had no effect. In striata the drug did not significantly affect ACh release although it showed a tendency to increase it. The ACh content in the three areas considered was not affected by tianeptine at above doses. The drug did not alter choline-o-acetyltransferase and acetylcholinesterase activities suggesting that it did not influence the cholinergic system through direct action on the ACh metabolism; furthermore, it did not influence the sodium-dependent high-affinity uptake of choline in striatum, cortex and hippocampus. Impairment of serotonergic (5-HT) neurotransmission by chemical lesion of the median raphe nucleus or by metergoline, a blocker of 5-HT receptors, antagonized the cholinergic effect of tianeptine. The involvement of the serotonergic system is specific because lesions of the noradrenergic dorsal bundle failed to prevent the inhibitory action of tianeptine. The present data suggest that 5-HT may mediate the effect of tianeptine on the cholinergic system in dorsal hippocampi.

Acetylcholine↗
PubMed1992

Susceptibility to seizures produced by chemical convulsants and maximal electric shock in rats after electrolytic lesions into the red nucleus.

Bilateral electrolytic lesions into the red nucleus (RN) of rat elicit an increase in susceptibility to seizures induced by pilocarpine, kainic acid, isoniazid, pentylenetetrazole, bicuculline and maximal electric shock (MES). It was also observed that carbachol-induced wet-dog shakes were increased in the RN-lesioned rats. The brain acetylcholine (ACh) and gamma-aminobutyric acid (GABA) concentrations were significantly decreased in the striatum and substantia nigra, respectively. There were no changes in electroencephalogram (EEG) recordings in the RN-lesioned group compared with sham-operated rats. Based on the results it is proposed that the RN is involved in the generalization and acceleration of seizure activity through the cholinergic and GABA-ergic system.

Acetylcholine↗
PubMed1992

Expression of GAL mRNA in rat hypothalamus: effect of frontal deafferentation and colchicine treatment.

The expression of galanin (GAL) mRNA was determined by in situ hybridization after frontal deafferentation and colchicine treatment in the rat hypothalamus. Frontal deafferentation significantly increased the signal in the paraventricular nucleus (PVN), the supraoptic nucleus (SON), and dorsomedial nucleus (DMN). Colchicine treatment induced a diffuse enhancement of GAL mRNA in hypothalamic nuclei. When the two treatments were combined there was an additivity of GAL mRNA expression in the previous hypothalamic nuclei and also in the arcuate nucleus (AN), where the single treatments did not modify the signal. These results suggest the regulation of GAL mRNA expression mediated by a multineuronal pathway, separate from the colchicine-induced GAL mRNA increase.

Afferent Pathways↗
PubMed1992

Endogenous dopamine facilitates striatal in vivo acetylcholine release by acting on D1 receptors localized in the striatum.

Intrastriatal application of the D1 antagonist SCH 23390 by two procedures, reverse dialysis (20 microM) and local injection (0.45 nmol per striatum), elicited a reduction in acetylcholine (ACh) release superimposable on that induced by systemic administration. The novel selective D1 antagonist SCH 39166 produced a similar decreasing effect on striatal ACh release on local injection (0.45 nmol per striatum). On the other hand, local application of SCH 23390 into the frontal cortices (0.45 nmol per side) failed to alter striatal ACh overflow, indicating that the drug does not diffuse out of its injection site to any significant extent. The dopamine release inducer d-amphetamine (2 mg/kg s.c.) and the dopamine uptake inhibitor cocaine raised ACh release like the D1 agonists. These effects were completely blocked by 10 microM SCH 23390 applied by reverse dialysis. The results suggest that D1 receptors regulating ACh release are located in the striatum.

Acetylcholine↗
PubMed1992

Dopamine depletion preferentially impairs D1- over D2-receptor regulation of striatal in vivo acetylcholine release.

The roles of D2 and D1 dopaminergic receptors on the regulation of striatal acetylcholine (ACh) release in vivo were examined for a period of 120 min after acute (2 h) or prolonged (16 h) depletion of brain dopamine (DA) by alpha-methyl-p-tyrosine. The reduction of DA transmission did not affect basal ACh output after 2 h but markedly lowered ACh release by 16 h (50%). Acute alpha-methyl-p-tyrosine pretreatment prevented the reduction of ACh release by the D1 antagonist SCH 23390 and its increase by the D2 antagonist, remoxipride, consistent with a drastic reduction of DA transmission at both DA receptors. However, 16 h after alpha-methyl-p-tyrosine, the effect of remoxipride on ACh release was restored, but SCH 23390 still had no effect, suggesting that the D2 inhibitory tone on ACh release had recovered, whereas the reduction of the D1 facilitatory influence persisted. The D1 facilitatory control of ACh neurotransmission thus appears to be more sensitive than the D2 inhibitory control to a reduction in DA transmission. The new model of DA-ACh interaction resulting from these data casts fresh light on the relationship between changes in DA transmission and extrapyramidal motor function.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1992

[Left ventricular false tendon: the most frequent cause of "innocent" murmur in childhood?].

BACKGROUND: The left ventricular false tendon (FT) is an anomalous fibrous or fibromuscular band stretching across the left ventricle. The false tendons extend from the septum to the left ventricular free wall or, more rarely, from the septum to a papillary muscle. The association between FT and innocent cardiac murmur has been pointed out. The aim of the present study was to assess the incidence of FTs in children with a murmur classified as innocent. METHODS: Two groups of subjects were selected. Group A consisted of 253 children with: 1) systolic ejection murmur; 2) normal electrocardiogram and 3) absence of clinical data suggesting cardiac disease. Group B consisted of 240 children clinically free of cardiac disease, and without any cardiac murmur. A FT was diagnosed by means of 2D echocardiogram whenever a linear band stretching across the left ventricular chamber was evident in at least two sections. RESULTS: One hundred and sixty-one children of group A (63.6%) reflected a left ventricular FT; only in 3 patients out of 161 the FT was associated with a small ventricular septal defect, whereas in 158 children the FT was the only abnormal finding. A normal echocardiogram was observed in 71 children (28.1%) of group A; whereas in 21 patients (8.3%) a congenital heart disease was diagnosed. In group B, only 33 subjects (13.8%) had a FT. The different incidence of FT in the two groups (63.6% versus 13.8%) was statistically significant (p less than 0.01). CONCLUSIONS: The study shows that about two thirds of children with innocent heart murmur reflect a left ventricular FT. Furthermore, FT is far more common in subjects with innocent cardiac murmur than in normal subjects. The relationship between FT and murmur thus appears very likely, although not definitely proven.

Adolescent↗
PubMed1991

M-15: high-affinity chimeric peptide that blocks the neuronal actions of galanin in the hippocampus, locus coeruleus, and spinal cord.

The 20-amino acid peptide M-15 binds with high affinity (IC50 approximately 0.1 nM) to 125I-labeled galanin (125I-GAL) binding sites in membranes from the ventral hippocampus, midbrain, and rat spinal cord. Receptor autoradiographic studies show that M-15 can displace 125I-GAL from all labeled sites. M-15 acts as a reversible high-affinity antagonist in blocking the inhibitory effects of GAL on the evoked release of acetylcholine in vivo in the hippocampus and on the GAL-induced hyperpolarization of locus coeruleus neurons in slices. M-15 also blocks the facilitatory effects of GAL on the spinal flexor reflex. Thus, the chimeric peptide M-15 [GAL-(1-13)-substance P-(5-11)amide] represents the first antagonist to the neuronal actions of GAL.

Acetylcholine↗
PubMed1991

Modulation of cortical in vivo acetylcholine release by the basal nuclear complex: role of the pontomesencephalic tegmental area.

Acetylcholine (ACh) release in vivo from rat cortices was determined by microdialysis either after injection of drugs into the basal nuclear complex (NBM) or after electrolytic lesion of the pontomesencephalic tegmental nucleus (PPT). Scopolamine (SCOP) (5-10 micrograms) increased and oxotremorine (10 micrograms) reduced cortical ACh release, indicating that an inhibitory mechanism operates within the area. The gamma-aminobutyric acid (GABA)ergic antagonist, picrotoxin (2.5 micrograms), by disinhibiting the cholinergic basocortical neurons, induced an increase that was not affected by SCOP. Acute lesion of the cholinergic PPT efferents to NBM raised cortical basal release. Thus, ACh released from the PPT terminals apparently modulates the function of basocortical neurons mainly through a polysynaptic link via GABAergic neurons.

Acetylcholine↗
PubMed1991

Pertussis toxin-sensitive G-protein mediates galanin's inhibition of scopolamine-evoked acetylcholine release in vivo and carbachol-stimulated phosphoinositide turnover in rat ventral hippocampus.

The effects of intracerebroventricular (i.c.v.) injections of pertussis toxin were investigated on the inhibitory action of galanin on acetylcholine release and phosphoinositide breakdown stimulated by muscarinic agents in rat ventral hippocampus. Pertussis toxin (0.6 micrograms, i.c.v., 96 h) counteracted the in vitro inhibitory effect of galanin (3.1 nmol) on phosphoinositide breakdown stimulated by carbachol without altering the stimulatory action of the cholinergic agonist on signal transduction, in miniprisms from rat ventral hippocampus. Pertussis toxin also abolished the in vivo effect of galanin on scopolamine-stimulated acetylcholine release in vivo but did not affect basal acetylcholine release. The results indicate that pertussis toxin-sensitive G-protein(s) mediates the galanin receptor regulation of pre- and postsynaptic cholinergic functions in the ventral hippocampus.

Acetylcholine↗
PubMed1991

Galanin reduces carbachol stimulation of phosphoinositide turnover in rat ventral hippocampus by lowering Ca2+ influx through voltage-sensitive Ca2+ channels.

The 29-amino-acid peptide galanin (GAL) caused concentration-dependent inhibition of the accumulation of 3H-inositol phosphates (3H-InsPs) induced by the muscarinic agonist carbachol (CARB; 10(-3)-10(-5) M) in the presence of 5 mM lithium, specifically in tissue miniprisms from rat ventral hippocampus. The inhibitory effect of GAL involved the mono-, bis-, tris-, and tetrakisphosphates formed during activation for 2 min of phospholipase C by CARB (1 mM) in the absence of lithium. GAL (1 microM) did not affect alpha-adrenergic or serotonergic type 2 receptor-mediated phosphoinositide (PI) breakdown in the same tissue. GAL by itself neither acted on basal levels of 3H-InsPs nor affected muscarinic receptors in binding studies. Blockade of the T-, N-, and L-types of voltage-sensitive calcium channel (VSCC) with 200 microM Cd2+ reduced muscarinic receptor-mediated PI breakdown by 50% and abolished the inhibitory effect of GAL (1 microM). Reduction of the extracellular Ca2+ concentration from 1.3 mM to 0.49 microM abolished the GAL inhibition of CARB-stimulated PI hydrolysis. Ca2+ influx promoted by 18 mM K+ depolarization or by 1 microM Bay K 8644, a selective agonist of the L-type VSCC, prevented the inhibitory effect of GAL. Blockade of the L-type VSCC with nifedipine (1 microM) potentiated the inhibitory effects of GAL without affecting muscarinic stimulation of PI breakdown.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

D1 and D2 dopaminergic regulation of acetylcholine release from striata of freely moving rats.

The effects of selective D1 and D2 dopaminergic agents on the extracellular acetylcholine (ACh) content in striata of freely moving rats were determined by the microdialysis technique. LY 171555, a selective D2 agonist, reduced ACh output by approximately 30% within 20 min at the dose of 0.2 mg/kg, i.p., whereas the D2 antagonists (-)-remoxipride (10 mg/kg, s.c.) and L-sulpiride (50 mg/kg, i.p.) induced maximal increases of approximately 50% within 10 and 20 min, respectively. In contrast, the D1 antagonist SCH 23390 (0.25 mg/kg, s.c.) decreased the extracellular ACh content by approximately 30% in 20 min, but lower doses--0.025 and 0.05 mg/kg--had no such effect. The stimulation of ACh release by LY 171555 was prevented by (-)-remoxipride but not by SCH 23390 (0.25 mg/kg, s.c.). In addition, the D1 agonist SKF 38393 failed to modify the ACh increasing effect of (-)-remoxipride. Thus, the D1 and D2 receptors subserve opposing functions on ACh release. The D1/D2 dopaminergic agonist R-apomorphine, at the does of 1 mg/kg, i.p., reduced ACh output by approximately 35% only when D1 receptors were blocked by SCH 23390 (0.025 mg/kg, s.c.). The results provide clear in vivo evidence of the tonic inhibition exerted by dopaminergic nigrostriatal input on the cholinergic system of the basal ganglia through D1 and D2 receptors.

Acetylcholine↗
PubMed1990

Activity of centrally administered galanin fragments on stimulation of feeding behavior and on galanin receptor binding in the rat hypothalamus.

Synthetic fragments of galanin 1-29 were administered intraventricularly or into the paraventricular nucleus of the hypothalamus for analysis of the critical amino acid sequence necessary to stimulate feeding behavior in rats. Galanin 1-29 and galanin fragment 1-16 significantly increased feeding at doses of 6 nmol microinjected into the lateral ventricles and 1 nmol microinjected into the hypothalamus. There was no significant effect of D-TRP2 galanin 1-16 microinjected into the hypothalamus, and no significant effect of galanin fragments 1-9, 10-20, 12-29, 17-29, or 21-29 microinjected intraventricularly, on food consumption. Synthetic fragments of galanin 1-29 were assayed for displacement of 125I-galanin 1-29 binding to rat hypothalamic membranes. The efficacies of the galanin fragments in the feeding paradigm were consistent with the relative affinities of these fragments for the hypothalamic galanin receptor in equilibrium binding experiments. The first 16 N-terminal amino acids appear to contain galanin agonist activity on increasing food consumption and to bind to the galanin receptor in the rat hypothalamus.

Animals↗