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M Marchi

Publications and source records attributed to M Marchi.

At least 91 records · Page 5Linked to original sources

Is the muscarinic receptor that mediates potentiation of dopamine release negatively coupled to the cyclic GMP system?

Dopamine (DA) terminals in rat corpus striatum and frontal cortex possess muscarinic receptors that mediate enhancement of the depolarization-evoked release of the catecholamine. The effects of the membrane-permeating cyclic guanosine monophosphate (cyclic GMP) analog 8-Br-cyclic GMP and of the phosphodiesterase inhibitor isobutylmethylxanthine (IBMX) on the muscarinic-induced increase of DA release were investigated in striatal synaptosomes prelabeled with [3H]DA and exposed in superfusion to 15 mM KCl and to acetylcholine (ACh). Preincubation of synaptosomes with 8-Br-cyclic GMP (10-200 microM) or with IBMX (200 microM) prevented the ACh-induced enhancement of [3H]DA release, without affecting the K+-evoked release of the [3H]amine. No significant decrease of the ACh effect was observed when 8-Br-cyclic GMP or IBMX were added concomitantly with ACh to the superfusion medium. The data suggest that stimulation of presynaptic muscarinic receptors on DA terminals may produce enhancement of 3H DA release through a decrease of the intraterminal cyclic GMP content.

1-Methyl-3-isobutylxanthine↗

Needle biopsy for muscle diagnosis and research: an Italian experience.

We report our experience of needle biopsy over the past two and a half, viz. 395 cases. We find that the technique meets the needs of diagnosis and research very satisfactorily. We describe its advantages over open biopsy and recommend it in preference to the latter, provided that the necessary technical skill for processing the sample is available.

Adolescent↗

[3]Pirenzepine binding in rat corpus striatum decreases after hemitransection of the nigro-striatal pathway.

The localization and pharmacologic characterization of muscarinic receptors possibly regulating the release of dopamine (DA) in rat corpus striatum were investigated by in vitro binding with [3H]pirenzepine ([3H]PZ) after hemitransection of the nigro-striatal pathway. DA levels in the corpus striatum ipsilateral to the lesion were substantially reduced by 66% compared with the unlesioned side after 8 days. The uptake of [3H]DA was also diminished by 63%. A significant decrease in the specific binding of [3H]PZ of 42% was seen in the corpus striatum ipsilateral to the lesion. The data indicate a loss of binding sites, whereas the lesion caused no change in the affinity constant for the muscarinic antagonist. The results support those previously obtained in studies of the muscarinic modulation of [3H]DA release from striatal synaptosomes and favor the idea that at least part of the muscarinic receptors regulating striatal DA release are localized on the nigro-striatal axon terminals and belong to the pirenzepine-sensitive subtype.

Animals↗

Multiple-dose pharmacokinetics in serum and sputum of sagamicin administered intramuscularly to patients.

Sagamicin is an aminoglycosidic antibiotic produced by Micromonospora sagamiensis, chemically related with gentamicin. Single- and multiple-dose pharmacokinetics have been investigated in patients affected by bronchopulmonary infections treated with 60 mg sagamicin i.m. every 12 h. The two concentration-time curves for sputum and serum are parallel; while there is no evidence of accumulation in the serum at the 7th day of treatment, sagamicin concentrations in the sputum are significantly higher on the 7th day, and this is also confirmed by a remarkable difference between the two AUC values. The good penetration power of sagamicin into sputum makes this antibiotic useful for the treatment of infections of the respiratory tract.

Aged↗

Soybean protein diet increases low density lipoprotein receptor activity in mononuclear cells from hypercholesterolemic patients.

The effect of two diets containing different protein sources (animal vs. soybean) on the low density lipoprotein (LDL) receptor activity was tested in freshly isolated mononuclear cells from 12 individuals with severe type II hyperlipoproteinemia. The two diets, both taken for 4 wk in a crossover design were of otherwise identical composition. During the soybean protein diet period, total cholesterol was reduced by 15.9% and LDL-cholesterol by 16.4%. The diet containing animal proteins exerted no significant change in plasma lipid levels vs. the baseline findings. The soybean diet regimen dramatically affected the degradation of LDL by mononuclear cells. Degradation was increased 16-fold vs. the basal activity and 8-fold compared with the standard low lipid diet with animal proteins. There was, however, no clear relationship between the reduction of total and LDL-cholesterolemia and the increased LDL degradation. These findings confirm similar data previously obtained in cholesterol-fed rats and suggest that some factor/s, most likely of a protein nature, may regulate the expression of lipoprotein receptors in peripheral cells, particularly when receptor activity is suppressed by experimental diets and/or spontaneous hypercholesterolemia.

Adult↗

Dicyclomine- and pirenzepine-sensitive muscarinic receptors mediate inhibition of [3H]serotonin release in different rat brain areas.

The effects of acetylcholine (ACh) on the release of [3H]5-hydroxytryptamine ([3H]5-HT) were investigated in synaptosomes prepared from rat cerebral cortex, hypothalamus and hippocampus and depolarized with 15 mM KCl under superfusion conditions. ACh inhibited the release of [3H]5-HT in all three brain areas. This effect was not modified by hexamethonium but was antagonized by atropine and by the non-classical antagonists pirenzepine and dicyclomine.

Acetylcholine↗

Studies on a possible functional coupling between presynaptic acetylcholinesterase and high-affinity choline uptake in the rat brain.

The relationships between presynaptic acetylcholinesterase (AChE) and high-affinity choline uptake (HACU) were investigated using a monolayer of rat cortex synaptosomes in superfusion conditions. The following sets of experiments were performed: determination of [3H]choline ([3H]Ch) uptake during superfusion with [3H]Ch; determination of [3H]Ch uptake during superfusion with acetylcholine (ACh) tritiated in the Ch moiety; evaluation of ACh hydrolysis during superfusion with ACh labelled in the acetate moiety; and comparison of the uptake of [3H]Ch generated by hydrolysis of [3H]ACh with that occurring during superfusion with [3H]Ch. Intact ACh was not taken up by superfused synaptosomes. The uptake of [3H]Ch during superfusion with 1 or 0.1 microM [N-methyl-3H]ACh was two-thirds of that occurring during superfusion with the same concentrations of [3H]Ch. The amount of [3H]Ch produced by hydrolysis during 16 min of superfusion was 1/25 of the amount passing through the synaptosomal monolayer during 16 min of superfusion with [3H]Ch. The results indicate that presynaptic AChE and HACU are located in close proximity to each other on the cholinergic terminal membrane, an observation suggesting the possibility of a functional coupling between the two mechanisms.

Acetylcholinesterase↗

GM1 monosialoganglioside inner ester induces early recovery of striatal dopamine uptake in rats with unilateral nigrostriatal lesion.

The experiments concerned the effect of parenteral administration of GM1 monosialoganglioside inner ester on the uptake of [3H]dopamine ([3H]DA) in synaptosomes prepared from the corpus striatum of rats with a unilateral lesion of the nigrostriatal pathway. In the animals treated with the ganglioside, starting on the 2nd day after lesion, the apparent Vmax of [3H]DA uptake (desipramine-insensitive) showed a marked recovery (from 10% to 33% of the controlateral side) as early as after 3 days of treatment, with no changes in the apparent Km values.

Animals↗

Activation of muscarinic receptors on striatal synaptosomes increases the release of endogenous dopamine.

The release of endogenous dopamine was investigated using rat striatal synaptosomes in superfusion. Depolarization with 15 mM KC1 evoked a release which was totally calcium-dependent. Also, the basal release of dopamine was in part dependent on the presence of calcium ions. Exogenous acetylcholine potentiated the K+-induced release of endogenous dopamine through the activation of receptors of the muscarinic type located on dopamine nerve terminals. Very similar results were obtained when the release of 3H-dopamine, previously taken up into striatal synaptosomes, was examined.

Acetylcholine↗

On the presence in the cerebral cortex of muscarinic receptor subtypes which differ in neuronal localization, function and pharmacological properties.

The existence in rat frontal cerebral cortex of subtypes of muscarinic receptors was investigated by using as a receptor-mediated functional response the release of neurotransmitters from isolated nerve endings. Synaptosomes prelabeled with [3H]choline or [3H]dopamine were depolarized with 15 mM KCl. Acetylcholine (ACh) concentration-dependently decreased the release of [3H]ACh and increased that of [3H]dopamine. Both actions of ACh were counteracted by the classical muscarinic antagonists atropine and quinuclidinyl benzylate. The two antagonists did not discriminate between the muscarinic presynaptic receptors sited on cholinergic terminals (muscarinic autoreceptors) and those located on dopamine nerve endings (muscarinic heteroreceptors). The apparent affinity (pA2) values for the two receptors were: 8.41 and 8.57 with atropine and 8.55 and 8.34 with quinuclidinyl benzylate. However, other muscarinic antagonists behaved differently. Dicyclomine strongly antagonized ACh at the heteroreceptors (pA2 = 8.69), whereas it was ineffective at the autoreceptors when tested at 5 microM. Pirenzepine had a similar behavior, although its affinity at the heteroreceptors was lower (pA2 = 6.33). In contrast, secoverine antagonized ACh at the autoreceptors with an affinity (pA2 = 7.58) higher than that showed at the heteroreceptors (pA2 = 6.51). The data support the existence in the frontal cortex of muscarinic receptors that are located on different neurons, mediate different functional responses and are pharmacologically distinguishable.

Acetylcholine↗

[Anesthesia and sickle cell disease].

Sickle cell anaemia is the most common hereditary haemoglobin pathology. It is found in either a homozygous or heterozygous form, associated in the latter case with other haemoglobinopathies. In view of the pathogenesis and the various related imbalances, amply confirmed by others, which can well prove disastrous, the pre, per and post-operative precautions to be adopted in such patients are assessed.

Acidosis↗

[Therapy and follow-up of breast cancer. Experiences in 11 years of observation].

Out of 1260 biopsies performed on neoplasias of the breast in 11 years' surgical practice, 463 (36,7%) malignant tumours were encountered. The surgical strategy in the latter cases was based on two basic parameters: a) the histological report on the intraoperative biopsy; b) the clinical stage (TNM). After surgery oncological treatment followed the now universal standard practice: --T1, T2, T3, N+, M0 and T4 independent of N or M: multiple chemotherapy for 6-12 months then periodic check ups as in N- cases. --M1: multiple chemotherapy, hormone and radiation treatment combined in various ways. The results obtained in terms of trouble free periods and survival are in line with reports in the literature including those describing a larger number of cases.

Breast Neoplasms↗

The functional recovery of damaged brain: the effect of GM1 monosialoganglioside.

In the present study the topology and the biochemical mechanisms underlying the functional recovery of the dopaminergic nigrostriatal system is further analyzed. Rats with unilateral hemitransection were treated with 30 mg/kg GM1 monosialoganglioside or with its internal ester derivative for different periods of time. GM1 enhances 3H-dopamine uptake in striatal synaptosomes of the lesioned side, and the enhancement of dopamine uptake precedes that of striatal tyrosine hydroxylase activity. The above biochemical effects are accompanied by changes in behavioral- and electrophysiological-related parameters. The effect of GM1 on striatal tyrosine hydroxylase of the lesioned side disappears when the ascending dopaminergic fibers are extensively lesioned. This suggests that the source of regrowing dopaminergic nerve terminals in the striatum of partially lesioned rats resides mainly in the intact axons remaining in the ipsilateral side. When GM1 is injected into partially lesioned rats kept in darkness, no effect on tyrosine hydroxylase activity is observed. This indicates that the mechanism through which GM1 acts involves a normal light-dark cycle.

Animals↗

Heterogeneity of presynaptic muscarinic receptors regulating neurotransmitter release in the rat brain.

The existence of multiple muscarinic receptors in the brain was investigated by using neurotransmitter release as a functional parameter and by comparing the effects of agonists and antagonists on three systems of release regulation mediated by presynaptic muscarinic receptors. The receptors selected as models for our experiments were: 1) the muscarinic autoreceptors mediating inhibition of acetylcholine release in the cortex; 2) the muscarinic autoreceptors present in the nerve endings of the hippocampus; and 3) the muscarinic presynaptic receptors mediating potentiation of striatal dopamine release (heteroreceptors). The experiments were performed by using rat brain synaptosomes in superfusion. Acetylcholine, oxotremorine and carbachol inhibited the release of [3H]acetylcholine evoked by 15 mM KCI in cortex and hippocampus and potentiated the K+-evoked [3H]dopamine release in the striatum. The concentration-response curves were similar in the three systems, the rank of potency being: acetylcholine greater than oxotremorine greater than carbachol. The effects of acetylcholine were counteracted by several muscarinic antagonists with different rank of potencies and different potency ratios. In particular, the rank of potencies for the drugs tested was: atropine greater than secoverine greater than stercuronium greater than pirenzepine at the autoreceptors, both in cortex and hippocampus; but it was: atropine greater than pirenzepine = secoverine greater than stercuronium, at the heteroreceptors in the striatum. Pirenzepine was 100 times more potent on heteroreceptors than on autoreceptors. Our results suggest the possibility of a differential activation or blockade of central muscarinic receptors by selective drugs.

Acetylcholine↗