Simultaneous determination of femtomole quantities of 5-hydroxytryptophan, serotonin and 5-hydroxyindoleacetic acid in brain using HPLC with electrochemical detection

Lacković, Zdravko; Parenti, Marco; Neff, Norton H.

doi:10.1016/0014-2999(81)90481-7

Cited by 62 publications

(8 citation statements)

References 10 publications

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“…They were killed 48 h after the last injection. The 5-HT content (measured by HPLC following the procedure described by Lackovich et al, 1981) tion sites, whereas the number of enzyme molecules is presumably unchanged by p-CPA. A transection of the fimbria-fornix tract, through which a great proportion of the noradrenergic and serotonergic fibers enter the hippocampus, and a selective chemical lesion of the serotonergic fibers by injecting i.c.v.…”

Section: Hippocampal Location Of the Serotonin Receptors Coupled Withmentioning

confidence: 99%

Serotonin‐Elicited Amplification of Adenylate Cyclase Activity in Hippocampal Membranes from Adult Rat

Barbaccia

Brunello

Chuang

et al. 1983

Journal of Neurochemistry

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The activity of the adenylate cyclase located in membranes prepared from hippocampus of adult rat can be stimulated by serotonin (5-HT) (Ka = 4 X 10(-7) M). The maximal effect is obtained with 10 microM 5-HT. Freezing of the tissue decreases the 5-HT stimulation; this stimulation is optimal in the presence of 82.5 mM Tris-maleate buffer (pH 7.4) and 50 microM GTP. The adenylate cyclase activity of membranes prepared from cortex, hypothalamus, and colliculi of adult rats is not significantly stimulated by 5-HT. Dopamine (DA) also stimulates adenylate cyclase located in hippocampal membranes; its effect can be blocked by haloperidol (10(-6) M), which fails to inhibit 5-HT stimulation. Moreover, p-chlorophenylalanine treatment for 2 weeks or selective lesion of 5-HT axons afferent to the hippocampus increases the Vmax of 5-HT stimulation, but fails to change that of DA stimulation. The 5-HT stimulation can be inhibited by metergoline, spiroperidol, and pizotyline (10(-6) M), but not by the same concentrations of mianserin, ketanserine, alprenolol, phenoxybenzamine, and mepyramine. The 5-HT stimulation of adenylate cyclase of hippocampal membranes can be mimicked by tryptamine, 5-methoxytryptamine, bufotenine, and to a lesser extent by LSD; N-methyltryptamine, N-methyltryptophan, and 5-hydroxytryptophan are inactive. Studies with kainic acid suggest that the 5-HT recognition site (5-HT1) linked to adenylate cyclase is located on the membrane of intrinsic hippocampal neurons.

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Section: Hippocampal Location Of the Serotonin Receptors Coupled Withmentioning

confidence: 99%

Serotonin‐Elicited Amplification of Adenylate Cyclase Activity in Hippocampal Membranes from Adult Rat

Barbaccia

Brunello

Chuang

et al. 1983

Journal of Neurochemistry

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“…To validate the use of blanks with fluoxetine, experiments were carried out with hippocampal minces prepared either from control sham-operated rats or from rats having a selective lesion of the 5HT terminals produced by 5,7-DHT. The selectivity of the lesion was assessed by measuring the hippocampal content of 5HT (25) and NE (26) in five rats taken at random from 40 that were injected with the neurotoxin. The brain 5HT content was decreased by about 80-85% in the rats with lesions, whereas the NE content was virtually unchanged in comparison to that of sham-operated rats.…”

mentioning

confidence: 99%

Modulation of neuronal serotonin uptake by a putative endogenous ligand of imipramine recognition sites.

Barbaccia¹,

Gandolfi²,

Chuang³

et al. 1983

Proc. Natl. Acad. Sci. U.S.A.

121

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Imipramine inhibits the serotonin uptake by binding with high affinity to regulatory sites of this uptake located on axons that release serotonin. The number of imipramine recognition sites located on crude synaptic membrane preparations is reduced by two daily injections of imipramine or desmethylimipramine for 3 weeks. When the binding sites for [3H]imipramine are down-regulated the Vma of the neuronal uptake of serotonin is increased. Moreover, in minces prepared from the brain hippocampus of rats receiving imipramine in a dose regimen that reduces the number of [3H]imipramine recognition sites, the efficiency of imipramine as a blocker of the serotonin uptake is diminished. Hence the high-affinity binding sites for [3H]imipramine may have a physiological role in modulation of serotonin reuptake. Probably this is mediated by an endogenous effector of these regulatory sites. A nonpeptidic constituent of rat brain capable of displacing [3H]imipramine from its high-affinity binding site and of inhibiting the serotonin uptake in a dose-related manner has been extracted and its partial purification is described.Imipramine and desmethylimipramine (DMI) have been used for longer than two decades to relieve the symptoms of depression (1, 2). Their capacity to block norepinephrine (NE) and serotonin (5-hydroxytryptamine; 5HT) uptake has been considered to be important for their therapeutic action, but when it was noted that imipramine and DMI block amine uptake almost instantaneously, whereas their antidepressant action occurs with a latency time of 1-2 weeks (1), the importance of the uptake inhibition in explaining their therapeutic action was deemphasized. Upon repeated daily administration to rats imipramine and a number of its congeners down-regulate the function of NE recognition sites in several brain structures (3-6); because the onset of this down-regulation and that of the antidepressant action are delayed with respect to the beginning of the treatment, it has been suggested that the NE response downregulation and the antidepressant action may be related (6). An additional tool to study the mechanism of the down-regulation of /3-adrenergic receptors became available when Langer and his colleagues reported that specific Na+-dependent and highaffinity binding sites for [3H]imipramine are located in crude synaptic membranes prepared from various structures of mammalian brains (7,8). The maximal number, Bmax, of [3H]imipramine binding sites is down-regulated by repeated injections of imipramine or DMI (9-11). These recognition sites are located on 5HT axon terminals (12)(13)(14) and appear to be anatomically and functionally associated with the 5HT uptake mechanism (15)(16)(17).In 1981 at a symposium on the mode of action of antidepressants we reported that the selective destruction of 5HT axons by 5,7-dihydroxytryptamine (5,7-DHT), which eliminates[3H]imipramine recognition sites, prevented the down-regulation of f3-adrenergic recognition sites elicited by two daily injections of DMI repeated for 3 wee...

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“…The brains and plasma samples were stored at 70 ~ until analysis. The concentrations of the large neutral amino acids were determined in plasma and whole brain according to procedures previously described (Lindroth et al, 1979;Eriksson and Carlsson, 1988), as were brain monoamines and their respective metabolites (Lackovic et al, 1981;Magnusson et al, 1980). The data on brain amino acids are presented as time-point means + SEM.…”

Section: Methodsmentioning

confidence: 99%

Diurnal rhythms in rat brain large neutral amino acids (LNAAs), monoamines and monoamine metabolites

Voog

Eriksson

1992

J. Neural Transmission

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To obtain reliable information on the diurnal rhythms in rat brain large neutral amino acid (LNAA) concentrations, animals were killed, in groups of six, every one h throughout one 24 h period. By using such short sampling intervals, it was possible to detect a statistically significant diurnal variation in the whole brain concentration of each LNAA and to give a more detailed description of these diurnal variations than previously presented. Furthermore, the diurnal variations in whole brain concentrations of the precursor amino acids, tyrosine and tryptophan, were compared with corresponding variations in the respective monoamines and their main metabolites. Similar diurnal patterns were demonstrated for tryptophan, serotonin and 5-hydroxyindoleacetic acid. No such correspondence was detected for tyrosine, dopamine, 3,4-dihydroxyphenylacetic acid and homovanillic acid.

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Simultaneous determination of femtomole quantities of 5-hydroxytryptophan, serotonin and 5-hydroxyindoleacetic acid in brain using HPLC with electrochemical detection

Cited by 62 publications

References 10 publications

Serotonin‐Elicited Amplification of Adenylate Cyclase Activity in Hippocampal Membranes from Adult Rat

Serotonin‐Elicited Amplification of Adenylate Cyclase Activity in Hippocampal Membranes from Adult Rat

Modulation of neuronal serotonin uptake by a putative endogenous ligand of imipramine recognition sites.

Diurnal rhythms in rat brain large neutral amino acids (LNAAs), monoamines and monoamine metabolites

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