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M Raiteri

Publications and source records attributed to M Raiteri.

At least 217 records · Page 12Linked to original sources
PubMed1986

Cholinergic terminals in rat hippocampus possess 5-HT1B receptors mediating inhibition of acetylcholine release.

The effects of 5-hydroxytryptamine (5-HT) on the release of [3H]acetylcholine ([3H]ACh) from rat hippocampal nerve endings were investigated using synaptosomes labelled with [3H]choline and depolarized in superfusion with 15 mM KCl. The release of [3H]ACh was concentration dependently inhibited by exogenous 5-HT. The concentration-response curve of 5-HT was shifted to the right in a parallel way by methiothepin. The 5-HT2 antagonists ketanserin or methysergide did not antagonize the effect of 5-HT. The 5-HT1 agonist 5-methoxy-3-[1,2,3,6-tetrahydropyridin-4-yl]-1H-indole (RU 24969) mimicked 5-HT, whereas the 5-HT1A selective agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) was ineffective. When used as a 5-HT1A/5-HT1B antagonist, (-)propranolol antagonized 5-HT whereas spiperone (a 5-HT1A displacer) did not. The 5-HT1C selective antagonist mesulergine was also ineffective towards 5-HT. It can be concluded that hippocampal cholinergic terminals are endowed with inhibitory 5-HT receptors which appear to belong to the 5-HT1B subtype.

Acetylcholine↗
PubMed1986

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↗
PubMed1986

Pharmacological characterization of release-regulating serotonin autoreceptors in rat cerebellum.

The release of [3H]5-hydroxytryptamine ([3H]5-HT) evoked by 15 mM KCl in superfused rat cerebellum synaptosomes was inhibited by 5-HT (pEC30 = 8.73). Methiothepin antagonized 5-HT (pA2 = 9.28); ketanserin, methysergide, cinanserin and spiperone were ineffective. The receptors involved were activated (pEC30 = 8.90) by the 5-HT1 agonist 5-methoxy-3-[1,2,3,6-tetrahydropyridin-4-yl]-1H-indole (RU 24969) X (-)Propranolol shifted to the right (pA2 = 8.05) the dose-response curve of 5-HT. The 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) was ineffective. In conclusion, autoreceptors are present on 5-HT nerve endings in rat cerebellum and appear to belong to the 5-HT1B subtype.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1986

Serotonin inhibits the depolarization-evoked release of endogenous glutamate from rat cerebellar nerve endings.

Glutamic acid (Glu) has been proposed as the neurotransmitter of cerebellar granule cells. 5-Hydroxytryptamine (5-HT) afferents project to the cerebellar cortex. The possible interaction between 5-HT and Glu was investigated by studying the effect of 5-HT on Glu release. The Ca2+-dependent depolarization-evoked release of endogenous Glu from superfused rat cerebellar synaptosomes was potently inhibited by 5-HT. Methiothepin, but not ketanserin, cinanserin or methysergide, antagonized 5-HT. It is concluded that the release of Glu can be modulated by 5-HT through receptors sited on Glu terminals. These receptors belong to the 5-HT1-type.

Animals↗
PubMed1986

A reinterpretation of tyramine sympathomimetic effect and tachyphylaxis.

In this commentary, the indirect sympathomimetic effect of tyramine and the phenomenon of tyramine tachyphylaxis are reinterpreted in terms of carrier-mediated exchange processes. Extracellular tyramine would exchange with intraterminal noradrenaline and, upon repeated tyramine administration, with a mixture of noradrenaline and tyramine progressively more enriched in the pharmacologically inactive amine.

Adrenergic Fibers↗
PubMed1986

Serotonin autoreceptor in rat hippocampus: pharmacological characterization as a subtype of the 5-HT1 receptor.

The 5-hydroxytryptamine (5-HT) autoreceptors mediating inhibition of [3H]5-HT release in rat hippocampus have been characterized pharmacologically in terms of 5-HT receptor subtype by using superfused synaptosomes depolarized with 15 mM KCl. Exogenous 5-HT inhibited in a concentration-dependent way (pEC30 = 8.74) the K+-evoked release of [3H]5-HT. Methiothepin shifted the concentration-response curve of 5-HT to the right (pA2 = 8.62). The 5-HT2 receptor antagonists, ketanserin, methysergide or spiperone were ineffective against 5-HT. The 5-HT1 receptor agonist, 5-methoxy-3-[1,2,3,6-tetrahydropyridin-4-yl]-1H-indole (RU 24969) mimicked 5-HT and was equipotent as an inhibitor of the release of [3H]5-HT. In contrast, the putative 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) was almost ineffective at 1 microM. Finally, (-)propranolol, used as a non-selective 5-HT1A/5-HT1B receptor antagonist, shifted to the right (pA2 = 7.91) the concentration-response curve of 5-HT whereas the 5-HT1C receptor antagonist mesulergine was ineffective. In conclusion, 5-HT nerve terminals of rat hippocampus possess autoreceptors which appear to belong to the 5-HT1B subtype.

Animals↗
PubMed1986

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↗
PubMed1986

Differential pharmacology and function of two 5-HT1 receptors modulating transmitter release in rat cerebellum.

The release of endogenous glutamate (GLU) elicited by depolarization of rat cerebellum synaptosomes was inhibited potently (pEC30 = 9.77) by 5-hydroxytryptamine (5-HT). The 5-HT action was antagonized by methiothepin (pA2 = 10.37); ketanserin, methysergide, cinanserin and spiperone were ineffective. Exogenous 5-HT also inhibited the release of [3H]-5-HT from cerebellar synaptosomes (pEC30 = 8.73). Methiothepin, but not ketanserin, methysergide, cinanserin or spiperone counteracted the inhibition (pA2 = 9.28). The receptors involved (presynaptic 5-HT heteroreceptors and autoreceptors) were activated by the 5-HT1 agonist RU 24969 (5-methoxy-3-[1,2,3,6-tetrahydropyridin-4-yl]-1H-indole) which showed comparable activity at the two receptor systems. (-)-Propranolol, used as a 5-HT1 antagonist, shifted to the right (pA2 = 8.05) the dose-response curve of 5-HT at the autoreceptors, but was ineffective at the receptors regulating GLU release. On the contrary, the 5-HT1A agonist 8-hydroxy-2-di-N-propylamino)tetralin activated the presynaptic heteroreceptors (pEC30 = 7.98), but was ineffective as a 5-HT autoreceptor agonist. The results allow the following major conclusions: 5-HT receptors are located on GLU terminals in rat cerebellum where they may modulate in an inhibitory way the release of GLU; 5-HT autoreceptors possibly involved in a negative feedback regulation of 5-HT release are present on cerebellar 5-HT nerve endings; 5-HT autoreceptors and heteroreceptors can be pharmacologically differentiated and appear to represent subtypes of the 5-HT1 receptor.(ABSTRACT TRUNCATED AT 250 WORDS)

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1985

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↗
PubMed1985

Alpha 2-adrenoceptors in rat hypothalamus and cerebral cortex: functional evidence for pharmacologically distinct subpopulations.

The presynaptic alpha 2-adrenoceptors regulating, respectively, [3H]noradrenaline and [3H]5-hydroxytryptamine release were compared in experiments with noradrenaline and clonidine as agonists and the two enantiomers of mianserin as antagonists in rat hypothalamic and cortical synaptosomes depolarized with 15 mM KCl. The affinity of clonidine was 10 times higher at the alpha 2-autoreceptors than at the alpha 2-heteroreceptors. (-)Mianserin antagonized noradrenaline at the heteroreceptors but not at the autoreceptors. In contrast, (+)mianserin did not discriminate between the two receptors. The results support the existence in the rat brain of subtypes of alpha 2-adrenoceptors having different neuronal location, function and pharmacological properties.

Animals↗
PubMed1985

Chronic clonidine induces functional down-regulation of presynaptic alpha 2-adrenoceptors regulating [3H]noradrenaline and [3H]5-hydroxytryptamine release in the rat brain.

Clonidine inhibited, through the activation of alpha 2 presynaptic receptors, the release of [3H]noradrenaline (pIC30 = 7.47) and [3H]5-hydroxytryptamine (pIC30 = 6.47) evoked by 15 mM KCl from superfused rat cerebral cortex synaptosomes. The natural agonist noradrenaline inhibited the K+-evoked release of the two [3H]amines less effectively after long-term (12 days) treatment with clonidine than after acute treatment. It can be concluded that chronic clonidine administration can induce down-regulation of both the alpha 2 presynaptic autoreceptors located on noradrenaline terminals and the alpha 2 presynaptic heteroreceptors located on serotonin terminals.

Animals↗
PubMed1985

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↗
PubMed1985

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↗
PubMed1984

Functional evidence that chronic drugs induce adaptive changes of central autoreceptors regulating serotonin release.

Following long-term in vivo treatment of rats with methiothepin (a serotonin autoreceptor antagonist) or with clorgyline (a monoamine oxidase A inhibitor) plus CGP 6085A (a selective serotonin uptake inhibitor), the release of [3H]serotonin evoked by high-K+ from the cortical synaptosomes was inhibited by exogenous serotonin respectively more or less than following acute treatment with the drugs. The autoreceptor subsensitivity disappeared 10 days after drug withdrawal. The results indicate that, after long-term blockade or stimulation, serotonin autoreceptors become respectively hyper- or hyposensitive towards serotonin.

Animals↗
PubMed1984

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↗
PubMed1984

Noradrenaline uptake inhibitors do not reduce the presynaptic action of clonidine on 3H-noradrenaline release in superfused synaptosomes.

The interaction between clonidine, as an agonist at the alpha 2-autoreceptors regulating noradrenaline release, and inhibitors of noradrenaline neuronal uptake was investigated in superfused synaptosomes, i.e. in conditions preventing accumulation of the released transmitter in the vicinity of presynaptic autoreceptors. Desipramine or cocaine did not release the inhibitory action of clonidine on the release of 3H-noradrenaline evoked by 15 mM KCl from rat cortex synaptosomes, even when the concentration ratio between uptake inhibitor and clonidine was very high. The present results do not support the hypothesis of an interaction between imidazolines and noradrenaline uptake inhibitors at the level of alpha 2-autoreceptors, or that of a functional coupling between presynaptic alpha 2-autoreceptors and noradrenaline uptake mechanism.

Animals↗