5‐hydroxytryptamine: The Effects of Impaired Synthesis on Its Metabolism and Release in Rat

Curzon, G.; Fernando, J.C.R.; Marsden, C.A.

doi:10.1111/j.1476-5381.1978.tb17275.x

Cited by 41 publications

(19 citation statements)

References 19 publications

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“…The concentrations of 5-HIAA in both tissue and basal dialysate and 5-HIAA changes on both NSD 1015 (see below) and K+ treatment were also decreased in proportion to each other but more markedly than the changes of 5-HT. The resultant increased 5-HT/5-HIAA ratios agree with previous findings on brains of rats given PCPA at dosages sufficient to deplete partially central 5-HT (Marsden & Curzon, 1976;Curzon et al, 1978;Dickinson & Curzon, 1983).…”

Section: Discussionsupporting

confidence: 82%

“…In our own laboratory, in vivo dialysis was used to study the release of brain 5-HT following its depletion by reserpine , to obtain direct evidence that the behavioural effects of p-chloroamphetamine (PCA) are mediated by release of 5-HT from the neuronal cytoplasm (Adell et al, 1989) and to show that the novel antidepressant, tianeptine, attenuated K + -evoked 5-HT release (Whitton et al, 1991). In the present study, brain 5-HT stores were partially depleted by means of the 5-HT synthesis inhibitor pchlorophenylalanine (PCPA) and in vivo dialysis used to determine the consequences for basal dialysate 5-HT concentration and K+-evoked 5-HT release, These investigations extend earlier findings on the effect of PCPA on behavioural responses to tryptophan (Marsden & Curzon, 1976) and to PCA (Curzon et al, 1978).…”

Section: Introduction Methodssupporting

confidence: 76%

“…These animals exhibited hyperlocomotion which was reversed by tryptophan in parallel with the degree of re-attainment of normal 5-HT levels. In contrast to these findings, when 5-HT was released by PCA, the decrease of behavioural response in PCPA-pretreated rats was greater than predictable from the fall of brain tissue 5-HT (Curzon et al, 1978). This result is explicable by a combined in vivo dialysis and behavioural study of the effect of PCA on reserpinetreated rats (Adell et al, 1989) which confirmed earlier in vitro evidence (Ross & Kelder, 1977) that PCA releases 5-HT, not from vesicles, but from the neuronal cytoplasm.…”

Section: Discussioncontrasting

confidence: 48%

“…Numerous behavioural experiments (Harvey et al, 1975;Marsden & Curzon, 1976;Curzon et al, 1978;Borbely et al, 1981) K+ stimulation all to similar degrees ( Table 2). The concentrations of 5-HIAA in both tissue and basal dialysate and 5-HIAA changes on both NSD 1015 (see below) and K+ treatment were also decreased in proportion to each other but more markedly than the changes of 5-HT.…”

Section: Discussionmentioning

confidence: 99%

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Effect of p‐chlorophenylalanine on release of 5‐hydroxytryptamine from the rat frontal cortex in vivo

O’Connell

Portas

Sarna

et al. 1991

British J Pharmacology

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1 Rats were given p-chlorophenylalanine (PCPA, 150mgkg-1, i.p.) to inhibit partially 5-hydroxytryptamine (5-HT) synthesis so that its concentration in the frontal cortex fell by about half. The effects of this treatment on frontal cortex dialysate 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) concentrations were determined before and after stimulation by increasing K+ concentration in the perfusion fluid by 100 mm for 20 min. Rates of 5-HT synthesis as indicated by the effects of 3-hydroxybenzylhydrazine (NSD 1015, 150mg kg-, i.p.) on frontal cortex tissue and dialysate 5-hydroxytryptophan (5-HTP) and dialysate 5-HIAA were also measured in rats that had not been stimulated with K+. 2 Dialysate 5-HT and 5-HIAA concentrations of both vehicle-and PCPA-treated rats fell into major (group 1) and minor (group 2) populations statistically distinguishable from each other by the high 5-HT and low 5-HIAA values of the latter group. 3 In group 1 animals, PCPA decreased both the dialysate 5-HT concentration and its rise following stimulation by K+ in proportion with the decrease of 5-HT in frontal cortex tissue. 5-HIAA fell more markedly than 5-HT and in similar proportion in both tissue and dialysate. The fall of dialysate 5-HIAA on stimulation by K+ was also attenuated to the same degree. The elevated 5-HT/5-HIAA ratios after PCPA treatment imply increased conservation of the depleted 5-HT stores. 4 PCPA decreased the above 5-HIAA values and the effects of NSD 1015 on tissue 5-HTP or dialysate 5-HIAA concentrations in similar proportion. However, PCPA had little effect on corresponding dialysate 5-HTP values. 5 The results are discussed with respect to relationships between synthesis, storage and release of 5-HT. They indicate that (under the conditions of the present study) the availability of 5-HT to receptors is directly proportional to total vesicular stores under both basal conditions and during neuronal firing.

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Section: Discussionsupporting

confidence: 82%

Section: Introduction Methodssupporting

confidence: 76%

Section: Discussioncontrasting

confidence: 48%

Section: Discussionmentioning

confidence: 99%

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Effect of p‐chlorophenylalanine on release of 5‐hydroxytryptamine from the rat frontal cortex in vivo

O’Connell

Portas

Sarna

et al. 1991

British J Pharmacology

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“…Under these circumstances newly synthesized 5-HT molecules are probably less available for release by PCA because of avid uptake by the partially emptied vesicles where, as indicated by high 5-HT/5-HIAA ratios (Curzon et al, 1978;, they are protected from metabolism. In contrast, reserpine disrupts vesicular storage so that newly synthesized 5-HT remains in the neuronal cytoplasm and is readily metabolised, as indicated by low 5-HT: 5-HIAA ratios (Table 1), but is available for release by PCA.…”

Section: Discussionmentioning

confidence: 99%

An in vivo dialysis and behavioural study of the release of 5‐HT by p‐chloroamphetamine in reserpine‐treated rats

Adell

Sarna²,

Hutson

et al. 1989

British J Pharmacology

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1 Reserpine (2.5mg kg-i.p.) decreased rat brain 5-hydroxytryptamine (5-HT) by 86% 24 h later but most components of the 5-HT-dependent behavioural syndrome induced by pchloroamphetamine (PCA, 5mgkg-'i.p.) or 5-methoxy-N,N-dimethyltryptamine (5-MeODMT, 5 mg kg -ti.p.) over 1 h after administration were unaffected. However, Straub tail was increased after giving PCA or 5-MeODMT and head weaving was decreased after giving 5-MeODMT. 2 Frontal cortex extracellular 5-HT concentrations of vehicle pretreated rats before injection of PCA, as calculated from dialysate 5-HT concentrations, were about 1/1000th of corresponding brain values. Extracellular 5-hydroxyindoleacetic acid (5-HIAA) and brain values were comparable with each other. Dialysate 5-HT increased after PCA with peak values at 20-40min. 3 Reserpine pretreatment reduced dialysate 5-HT concentration before PCA was given but the net increase (AUC) over the 1 h after PCA did not differ significantly from that seen in animals pretreated with vehicle. Dialysate 5-HIAA values slowly decreased after PCA injection in both reserpine and vehicle pretreated groups. 4 The results suggest that PCA causes the 5-HT syndrome by releasing 5-HT from the neuronal cytoplasm but that physiological release of 5-HT occurs from vesicular stores.

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Dopamine and serotonin turnover rate in the retina of rabbit, rat, goldfish, and Eugerres plumieri: Light effects in goldfish and rat

Lima

Urbina

1994

J of Neuroscience Research

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The concentration of dopamine, and its metabolites 3,4-dihydroxyphenylacetic and homovanillic acids, as well as serotonin and its metabolite 5-hydroxyindoleacetic acid, were determined in the retina of two teleosts, C. auratus (goldfish) and E. plumieri (mojarra), and two mammals, R. norvegicus (rat) and O. cuniculus (rabbit). The turnover rate of these monoamines were investigated in the four species by the calculation of the ratio monoamine/metabolite as an indirect index, and in goldfish and rat by the inhibition of the synthesis with alpha-methyl-p-tyrosine or p-chlorophenylalanine, by the increase in dopamine or serotonin by the corresponding precursors, 3,4-dihydroxyphenylalanine or 5-hydroxytryptophan, and by inhibition of monoaminooxidase with pargyline. The modulation by light and dark stimulation was studied in the goldfish and the rat. Differences in the concentration and turnover rate were observed among the species. Serotonin concentration was higher in the teleosts. The administration of inhibitors of dopamine and serotonin synthesis differentially decreased the levels of the monoamines in the retina of goldfish and rat. The rate of formation of dopamine and serotonin by the corresponding precursors was much higher in the goldfish than in the rat. Pargyline administration decreased 3,4-dihydroxyphenylacetic and 5-hydroxyindoleacetic acids at different rates and time dependency in the retina of goldfish and rat. Dopamine and serotonin concentration did not exhibit high modifications by the inhibitor, suggesting the function of regulatory mechanisms or additional effect of pargyline at other sites different from monoaminooxidase.(ABSTRACT TRUNCATED AT 250 WORDS)

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5‐hydroxytryptamine: The Effects of Impaired Synthesis on Its Metabolism and Release in Rat

Cited by 41 publications

References 19 publications

Effect of p‐chlorophenylalanine on release of 5‐hydroxytryptamine from the rat frontal cortex in vivo

Effect of p‐chlorophenylalanine on release of 5‐hydroxytryptamine from the rat frontal cortex in vivo

An in vivo dialysis and behavioural study of the release of 5‐HT by p‐chloroamphetamine in reserpine‐treated rats

Dopamine and serotonin turnover rate in the retina of rabbit, rat, goldfish, and Eugerres plumieri: Light effects in goldfish and rat

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