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Biomedical subjects

M Raiteri

Publications and source records attributed to M Raiteri.

At least 235 records · Page 13Linked to original sources
PubMed1984

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↗
PubMed1984

Is there a functional linkage between neurotransmitter uptake mechanisms and presynaptic receptors?

The possibility of interaction between neurotransmitter uptake mechanisms and presynaptic receptors regulating transmitter release was investigated using rat brain synaptosomes in superfusion. Various conditions were considered including: absence of substrate for the uptake with uptake potentially operative; absence of substrate and presence of uptake inhibitors; and uptake activated by added substrate, with or without uptake inhibitors. The release of [3H]-5-hydroxytryptamine ([3H]-5-HT) evoked by 15 mM KCl from cerebral cortex synaptosomes was inhibited by lysergic acid diethylamide. The 5-HT uptake inhibitors citalopram and chlorimipramine did not affect the inhibitory action of lysergic acid diethylamide. Clonidine decreased both the K+-evoked release of [3H]norepinephrine and that of [3H]-5-HT in cortical synaptosomes through the activation of presynaptic alpha-2 adrenoceptors. In superfusion conditions, the action of clonidine on [3H]norepinephrine release was not antagonized by the norepinephrine uptake inhibitors desipramine or cocaine; similarly, the inhibition of [3H]-5-HT release was unaffected when 5-HT uptake was blocked. The K+-evoked release of [3H]dopamine from striatal nerve terminals was potentiated by acetylcholine (ACh) through the activation of muscarinic presynaptic receptors. The action of ACh was not modified by the presence of nomifensine, a dopamine uptake inhibitor. Finally, in superfused cortical synaptosomes, the block of the high-affinity uptake of choline by hemicholinium-3 had no effect on the muscarinic autoreceptor-mediated inhibition of [3H]ACh release by ACh. Altogether the present results do not support the previously proposed idea that in nerve terminals a functional coupling may exist between uptake mechanisms and presynaptic receptors.

Acetylcholine↗
PubMed1983

Is acetylcholine release from striatal nerve endings regulated by muscarinic autoreceptors?

The presence in cholinergic nerve endings of muscarinic autoreceptors regulating the release of acetylcholine elicited by depolarizing stimuli was investigated in different areas of the rat brain. Synaptosomes prepared from cerebral cortex, hippocampus or corpus striatum were prelabeled with [3H]choline and the inhibitory effect of exogenous acetylcholine on the Ca2+-dependent release of [3H]acetylcholine evoked by 15 mM KCl was analyzed by superfusion. While acetylcholine was equally active in reducing its own release in hippocampus and cortex, it was much less effective in striatal synaptosomes. In contrast the values of several presynaptic cholinergic parameters ([3H]choline uptake, [3H]acetylcholine synthesis and release) were the highest in the striatum. Since experiments with slices showed that autoregulation of acetylcholine release through muscarinic receptors appeared to occur as efficiently in the striatum as in the two other areas, the present results suggest that in the striatum the autoregulation of acetylcholine release may not necessarily require the activation of autoreceptors located on cholinergic nerve terminals.

Acetylcholine↗
PubMed1983

Differential blockade by (-)mianserin of the alpha 2-adrenoceptors mediating inhibition of noradrenaline and serotonin release from rat brain synaptosomes.

Mianserin and its two enantiomers were studied as antagonists of the alpha 2-adrenoceptors mediating inhibition of noradrenaline and 5-hydroxytryptamine release in rat brain cortex. The inhibitory effect of exogenous noradrenaline on the release of 3H-noradrenaline evoked by 15 mM KCl from superfused cortical synaptosomes was antagonized by racemic mianserin and by (+)mianserin; the (-)enantiomer was ineffective. In contrast, both (+)mianserin and (-)mianserin antagonized the inhibitory effect of noradrenaline on the release of 3H-5-hydroxytryptamine. The results suggest that the alpha 2-autoreceptors on noradrenergic nerve endings differ from the alpha 2-adrenoceptors located on serotoninergic terminals.

Adrenergic alpha-Antagonists↗
PubMed1983

Calcium-dependent [3H]acetylcholine release and muscarinic autoreceptors in rat cortical synaptosomes during development.

A number of presynaptic cholinergic parameters (high affinity [3H]choline uptake, [3H]acetylcholine synthesis, [3H]acetylcholine release, and autoinhibition of [3H]acetylcholine release mediated by muscarinic autoreceptors) were comparatively analyzed in rat brain cortex synaptosomes during postnatal development. These various functions showed a differential time course during development. At 10 days of age the release of [3H]acetylcholine evoked by 15 mM KCl from superfused synaptosomes was Ca2+-dependent but insensitive to the inhibitory action of extrasynaptosomal acetylcholine. The muscarinic autoreceptors regulating acetylcholine release were clearly detectable only at 14 days, indicating that their appearance may represent a criterion of synaptic maturation more valuable than the onset of a Ca2+-dependent release.

Acetylcholine↗
PubMed1983

Functional evidence for two stereochemically different alpha-2 adrenoceptors regulating central norepinephrine and serotonin release.

The effects of norepinephrine and of various alpha adrenoceptor antagonists on the depolarization-evoked release of norepinephrine and 5-hydroxytryptamine were studied in nerve terminals isolated from rat cerebral cortex, preincubated with the radioactive amines and exposed during superfusion to 15 mM KCI. Exogenous norepinephrine inhibited in a concentration-dependent way both the release of norepinephrine and that of serotonin. The inhibitory effect of norepinephrine was antagonized by yohimbine and mianserin, but not by prazosin, indicating the involvement of alpha-2 adrenoceptors. The two enantiomers of mianserin were examined as alpha-2 adrenoceptor antagonists in the two release systems. Only (+)-mianserin was an effective antagonist at the alpha-2 autoreceptors mediating regulation of norepinephrine release; (-)-mianserin was inactive. In contrast, both enantiomers antagonized exogenous norepinephrine at the alpha-2 adrenoceptors regulating 5-hydroxytryptamine release. It can be concluded that the alpha-2 adrenoceptors which regulate, respectively, norepinephrine and serotonin release in the cerebral cortex are located on presynaptic nerve terminals and represent two stereochemically different subtypes of alpha-2 adrenoceptors.

Animals↗
PubMed1982

Presynaptic muscarinic receptors increase striatal dopamine release evoked by "quashi-physiological" depolarization.

The effects of acetylcholine on the release of [3H]dopamine was studied in superfused rat striatal synaptosomes prelabeled with the radioactive amine. The results confirm the presence of muscarinic presynaptic receptors mediating potentiation of the spontaneous release of the catecholamine. However, under depolarizing conditions, the release of dopamine evoked by 15 mM KC1 was increased by the activation of muscarinic receptors and not decreased, as previously found in striatal synaptosomes or slices depolarized with higher (50-60 mM) KC1 concentrations.

Acetylcholine↗
PubMed1982

Noradrenaline inhibits central serotonin release through alpha 2-adrenoceptors located on serotonergic nerve terminals.

The effect of noradrenaline on the depolarization-evoked release of 3H-5-hydroxytryptamine was investigated in superfused synaptosomes prepared from rat cortex and hippocampus and prelabelled with the radioactive indoleamine. Noradrenaline reduced in a concentration-dependent way the release of 3H-5-hydroxytryptamine elicited by 15 mM KCl. The inhibition was counteracted by the alpha-adrenoceptor antagonists phentolamine or yohimbine, but not by prazosin. The results indicate that, in rat brain, the inhibition of 5-hydroxytryptamine release by noradrenaline is mediated by adrenoceptors of the alpha 2-type localized on the terminal serotonergic fibres.

Animals↗
PubMed1981

Autoregulation of acetylcholine release in isolated hippocampal nerve endings.

The existence of presynaptic autoreceptors modulating acetylcholine release from central cholinergic nerve endings was investigated by using rat hippocampal synaptosomes in a superfusion system. The presence of exogenous acetylcholine, carbachol or oxotremorine in the superfusion fluid produced a dose-dependent inhibition of the release of [3H]acetylcholine elicited by 15 mM KCl in synaptosomes prelabeled with tritiated choline. The inhibition was counteracted by atropine. Another well known muscarinic agonist, bethanechol, had no effect on [3H]acetylcholine release. Our results indicate that central cholinergic nerve terminals possess autoreceptors of the muscarinic type for the control of acetylcholine release. Moreover, differences seem to exist between pre-and postsynaptic muscarinic receptors in the central nervous system.

Acetylcholine↗
PubMed1981

Enhancement by GABA of glutamate depolarization-induced release from cerebellar nerve endings.

Cerebellar synaptosomes were superfused in the presence of D-[3H]aspartate (to label the glutamate 'reuptake pool') and [14C]glutamine (to label the 'new synthesis pool'). The depolarization-induced release of D-[3H]aspartate and of newly synthesized [14C]glutamate were potentiated by low concentrations of GABA (2--20 microM) or muscimol. The effect was probably mediated by the interaction of GABA with presynaptic GABA receptors localized in 'glutamergic' nerve endings, since it was antagonized by the GABA antagonists picrotoxin and bicuculline.

Animals↗