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M Raiteri

Publications and source records attributed to M Raiteri.

At least 253 records · Page 14Linked to original sources
PubMed1980

Dopamine biosynthesis is regulated by the amine newly recaptured by dopaminergic nerve endings.

The synthesis of dopamine from labeled tyrosine (but not from labeled DOPA) in rat striatal synaptosomes was effectively inhibited by exogenous dopamine only when the amine was allowed to enter the nerve endings. In the presence of the uptake blocker nomifensine, extracellular dopamine was almost inactive. The evolution of 14CO2 from [14C]tyrosine was consistently higher when synaptosomes were 'incubated' in the presence of nomifensine than in its absence. This effect disappeared when synaptosomes were 'superfused' with labeled tyrosine (with or without nomifensine) in conditions in which dopamine reuptake cannot occur. The monoaminoxidase inhibitor pargyline inhibited 14CO2 evolution from [14C]tyrosine. However, the effect was almost abolished if dopamine reuptake was prevented (by nomifensine or in superfusion). Our results suggest that dopaminergic nerve endings do not possess autoreceptors controlling dopamine synthesis. In the present paper it is proposed that the regulation of dopamine synthesis occurs through inhibition of tyrosine hydroxylase, according to the classical and end-product concept; however, the function of 'end-product' would be primarily exerted by the amine newly taken up by the nerve terminals.

Animals↗
PubMed1980

Evidence for a similar compartmentation of recaptured and endogenously synthesized dopamine in striatal synaptosomes.

The aim of the present study was to compare the release pattern of [3H]dopamine ([(3H]DA) originated from [3H]tyrosine or by uptake in striatal synaptosomes. Synaptosomes prelabeled either with [3H]DA or with [3H]tyrosine were superfused in three conditions stimulating DA release by different mechanisms: (1) depolarization with high K+ (2) inversion of the NA+ gradient across the plasma membrane; (3) exposure to d-amphetamine. Since DA contained in different pools may exit from nerve endings by different processes, DA release was analyzed in the presence or in the absence of nomifensine which allows discrimination between carrier-mediated and carrier-independent processes. The pattern of DA release in the three conditions tested was idential, whether [(3)H]DA originated from synthesis or from uptake. Nomifensine did not affect the high-K+-induced release and inhibited that induced by the other two stimuli. The results suggest that newly synthesized and recaptured DA have similar compartmentation in nerve endings.

Animals↗
PubMed1980

A reevaluation of veratridine as a tool for studying the depolarization-induced release of neurotransmitters from nerve endings.

The effect of veratridine on neurotransmitter release was studied using rat brain synaptosomes superfused at 37 degrees C. Veratridine (5-75 microM) caused a concentration-dependent release of [3H]GABA from prelabeled synaptosomes in the presence of 2.7 mM Ca2+. In the whole range of veratridine concentrations, the release of [3H]GABA elicited by the drug was substantially increased rather than decreased in the absence of Ca2+ or with Ca2+ concentrations of 0.45 and 0.9 mM. The release of the amino acid was inhibited more by 5.4 mM than by 2.7 mM Ca2+. The effect on endogenous (chemically measured) GABA was similar to that on [3H]GABA. The inhibitory effect of Ca2+ on the veratridine-induced release of [3H]GABA was consistently seen in a variety of experimental conditions except one, namely when the experiment was run at room temperature (22-23 degrees C) rather than at physiological temperature (37 degrees C). In fact, at 22-23 degrees C the release of GABA evoked by the alkaloid was somewhat potentiated by Ca2+. At 37 degrees C, glutamate appeared to behave similarly to GABA, whereas the veratridine-induced release of [3H]noradrenaline and [3H]dopamaine was largely Ca2+-dependent. The mechanism of the release of transmitters elicited by veratridine is discussed. It is concluded that the evoked release of GABA and glutamate is due more to the veratridine-induced depolarization (Na+ influx) than to the accompanying influx of Ca2+, and it is suggested that the inhibitory effect of Ca2+ on the overall release of amino acids is due to the antagonism exerted by the divalent cation on the veratridine action at the Na+ channel. In contrast, in the case of catecholamines, the influx of Ca2+ would have a prominent role in triggering exocytotic release, whereas the depolarization itself would have slight or no importance.

Animals↗
PubMed1979

Differential binding of antidepressants to noradrenaline and serotonin transport sites in central nerve endings.

Imipramine and mianserin are equipotent inhibitors of noradrenaline (NA) uptake in synaptosomes. However, after in vivo administration, NA uptake was inhibited only in synaptosomes from imipramine-treated rats, suggesting that imipramine, or its metabolite desipramine, binds to the NA carrier in a manner outlasting the preparation of synaptosomes, whereas mianserin is washed away. To evaluate binding to the NA carrier, synaptosomes prelabeled with 3H-NA were pretreated with an antidepressant and the release of 3H-NA was then stimulated with unlabeled NA. Any reduction of release was taken as an indication of binding. Pretreatment with desipramine, but not with imipramine or mianserin, reduced 3H-NA release suggesting that desipramine is responsible for NA uptake inhibition in synaptosomes from imipramine-treated rats. Transformation of tertiary into secondary amines seems to be crucial for binding to the NA carrier, as confirmed by the stronger binding of nortriptyline and chlordesipramine compared to amitryptiline and chlorimipramine, respectively. In contrast, tertiary amines bound more strongly than secondary amines to the serotonin carrier. Adult and 8-day old synaptosomes showed similar binding properties towards imipramine and desipraine.

Animals↗
PubMed1979

Serotonin release is modulated by presynaptic autoreceptors.

The existence of presynaptic autoreceptors controlling the release of 5-hydroxytryptamine (5HT) from serotonergic nerve endings was investigated utilizing superfused hypothalamic synaptosomes. Extracellular 5HT reduced the high K+-induced release of previously accumulated 3H-5HT. The central 5HT receptor blocker methiothepin counteracted the inhibitory effect of 5HT. Other 5HT antagonists (cyproheptadine, methysergide and mianserin) were inactive and may therefore act preferentially at the postsynaptic receptors.

Animals↗
PubMed1978

Modulation of gamma-aminobutyric acid transport in nerve endings: role of extracellular gamma-aminobutyric acid and of cationic fluxes.

The aim of the present study was to elucidate the possible functional significance of gamma-aminobutyric acid (GABA) homoexchange at nerve endings. Using synaptosomes from adult rat cerebrum, we found that a number of conditions altering cationic fluxes produced a concomitant change in the stoichiometry of GABA homoexchange, In fact, exogenous GABA (10 muM), while not causing net release of intrasynaptosomal GABA in standard conditions, triggered a large net GABA release in the presence of veratridine, Na(+)-K(+)-ATPase inhibitors, or the ionophore A23187, superimposed on that due to the various agents tested alone. This extra release was mediated by the membrane carrier, being largely inhibited by the GABA carrier-blocker L-diaminobutyric acid. The altered stoichiometry of GABA homoexchange observed under these conditions (efflux > influx) appeared to be coupled to the influx of Na(+) (or of Ca(2+)), rather than determined by the establishment of a high intrasynaptosomal [Na(+)]. Under conditions of reversed Na(+) flux (Na(+) efflux), the GABA outward/inward flux ratio was also reversed, and the stoichiometry of GABA homoexchange was in favor of net influx. The possible contribution of K(+) to the effects observed is also discussed. It is concluded that the GABA transport system of nerve endings is susceptible to fine modulation by changes in cationic fluxes similar to those occurring in vivo during depolarization and repolarization. These fluxes may have a prominent role in determining the direction of net GABA transport in GABA-ergic nerve terminals of the living brain.

Aminobutyrates↗
PubMed1978

Release of dopamine from striatal synaptosomes.

The mechanisms of dopamine (DA) release central nerve endings have been investigated utilizing superfused rat striatal synaptosomes. Nomifensine was selected as a tool to discriminate between release mediated by the DA carrier and release occurring independently of the carrier. The following conclusions can be drawn from the results obtained: 1) Alterations of the sodium gradient across the synaptosomal membrane, induced by omission of extracellular Na+ or by ouabain, enhanced the release of 3H-DA from prelabeled synaptosomes. The release was blocked by nomifensine and therefore it was carrier-mediated. 2) The release of DA elicited by amphetamine and related phenylethylamines was nomifensine-sensitive, suggesting that the released DA existed from synaptosomes through the membrane carrier. 3) Depolarization of synaptosomes by high K+ triggered the release of both "newly taken up" and "newly synthesized" DA. 4) The calcium-dependent release of DA (induced by high K+, veratridine of by the ionophore A23187) was not affected by the carrier blocker nomifensine and may occur by an exocytic-like process. 5) The effects of apomorphine and neuroleptics on the stimulus-evoked release of DA do not support the existence of a presynaptic receptor-mediated inhibitory control of DA release identical to that described for noradrenaline.

Animals↗
PubMed1977

Effect of sympathomimetic amines on the synaptosomal transport of noradrenaline, dopamine and 5-hydroxytryptamine.

The interaction of sympathomimetic amines with the transport of 3H-noradrenaline (3H-NE), 3H-dopamine (3H-DA) and 3H-5-hydroxytryptamine (3H-5-HT) were investigated in rat hypothalamic (3H-NE) and striatal (3H-DA) and 3 H-5-HT) synaptosomes. Modifications in the phenylethylamine structure led to changes in activity towards biogenic amine uptake and release: (a) the introduction of a beta-OH group led to compounds less active in inhibiting uptake and stimulating release of 3H-NE, 3H-DA and 3H-5-HT, with the exception of 3H-NE release which was stimulated more by unlabeled 1-NE than by DA; (b) the introduction of phenolic-OH groups always led to compounds which were stronger uptake inhibitors and releasers of the three biogenic amines; (c) the alpha-methylation increased the potency towards uptake inhibition and release stimulation, with the exception of 3H-NE release: in fact, the releasing activity of phenylethylamine was suppressed by alpha-methylation; (d) the introduction of a -Cl group in the para position selectively potentiated the effects on 3H-5-HT uptake and release and generally depressed those on catecholamine transport.

Animals↗