Model of brain serotonin metabolism. II. Physiological interpretation

Tracqui, Philippe; Morot-Gaudry, Y.; Staub, J. F.; Brézillon, Patrick; Perault-Staub, A. M.; Bourgoin, S.; Hamon, M.

doi:10.1152/ajpregu.1983.244.2.r206

Cited by 11 publications

(9 citation statements)

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“…The essential similarity of the time courses for 5-HIAA in the CSF and brain is consistent with the model of Burns et al (1976) which indicated that 5-HIAA in rat brain and ventricles are in rapid equilibrium, that it leaves brain essentially exclusively via the CSF, and that the fluid in the ventricles is transported to the cisterna magna and subarachnoid spaces in a relatively short time, i.e., 4 min. More recent model studies in the mouse (Tracqui et al, 1983) are consistent with these conclusions.…”

Section: Discussionsupporting

confidence: 71%

Monitoring the Effect of a Tryptophan Load on Brain Indole Metabolism in Freely Moving Rats by Simultaneous Cerebrospinal Fluid Sampling and Brain Dialysis

Hutson¹,

Sarna²,

Kantamaneni³

et al. 1985

Journal of Neurochemistry

120

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Rats were given L-tryptophan, 50 mg/kg i.p., and its concentration in the CNS was monitored in individual freely moving animals using repeated sampling of cisternal CSF and concurrent striatal dialysis. The 5-hydroxytryptamine metabolite 5-hydroxyindoleacetic acid (5-HIAA) was also measured. Results were compared with changes of central tryptophan and 5-HIAA concentrations in brains of rats killed at various times after administration of L-tryptophan, 50 mg/kg i.p. Tryptophan changes in CSF were proportionate to those in whole brain and followed essentially identical time courses. Results for the striatal dialysate and whole striatum also paralleled each other. Similarly, results for 5-HIAA showed proportionality between CSF and brain and between dialysate and striatum. The data obtained were used to determine pharmacokinetic data for individual rats, i.e., areas under curves for both tryptophan and 5-HIAA and half-lives for the decline of tryptophan. Kinetic parameters varied considerably from rat to rat. However, mean half-lives for tryptophan in CSF, brain, dialysate, and striatum were all comparable. Results in general show the value of repeated CSF sampling and intracerebral dialysis for concurrent monitoring of changes of indole metabolism in the whole brain and a specific brain region, respectively. The methods should be suitable for the continuous monitoring of changes of central transmitter metabolism in parallel with observation of behavior following environmental or dietary changes or drug administration. They also should be of use in the investigation of drug kinetics in the CNS.

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Section: Discussionsupporting

confidence: 71%

Monitoring the Effect of a Tryptophan Load on Brain Indole Metabolism in Freely Moving Rats by Simultaneous Cerebrospinal Fluid Sampling and Brain Dialysis

Hutson¹,

Sarna²,

Kantamaneni³

et al. 1985

Journal of Neurochemistry

120

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“…The difference between the in vivo K, value and the in vitro K, value reflects enhanced dissociation from the protein-binding site, and this phenomenon has been termed "plasma proteinmediated transport" (PMT). The PMT phenomenon has been observed by a number of different laboratories (5, 7, 15,67,68,79,152,[260][261][262]280) in addition to those cited in Table 14.5.…”

Section: 5)mentioning

confidence: 96%

Targeted Delivery of Hormones to Tissues by Plasma Proteins

Pardridge

1998

Comprehensive Physiology

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The sections in this article are: Organ Physiology of Solute Exchange Through Capillary Walls Quantitation of Capillary Solute Transport: Kety‐Renkin‐Crone Equation Capillary Geometry, Organ Blood Flow, and Capillary Transit Times Capillary Membrane Permeability Capillary Physiology of Steroid and Thyroid Hormone Transport Plasma Protein–Binding Kinetics Dissociation‐Limited Transport Enhanced Dissociation Mechanism of Plasma Protein–Mediated Transport Transcapillary Transport of Protein–Hormone Complex Physiology‐Based Model of Cellular Bioavailable Hormone Experimental Attempts to Measure Free Cellular Hormone Molecular Physiology of Hormone‐Binding Plasma Proteins Albumin Prealbumin (Transthyretin) Thyroid Hormone–Binding Globulin Corticosteroid‐Binding Globulin Sex Hormone–Binding Globulin α 1 ‐Acid Glycoprotein (Orosomucoid) Summary

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“…Decreases in ECF 5-HIAA in a variety of brain regions have previously been reported to occur in response to these treatments (De Simoni et al, 1988;KalCn et al, 1988;Auerbach et al, 1989;Carboni and Di Chiara, 1989;Laferrere and Wurtman, 1989;Pei et al, 1989;Schwartz et al, 1989;Matos et al, 1990). This latter phenomenon may represent increased transfer of newly synthesized cytoplasmic 5-HT into a releasable pool (K') or increased translocation of that pool (fenfluramine) such that 5-HT is released from the terminal before degradation by intraneuronal MA0 (Shields and Eccleston, 1972;Tracqui et al, 1983;Auerbach and Lipton, 1985;Kuhn et al, 1985;Adell et al, 1989). The lack of a change in ECF 5-HIAA with these treatments in neonatally 6-OHDA-treated rats may reflect an increased ability of synthesis to match demands for release in these animals.…”

Section: Jmentioning

confidence: 97%

In Vivo Neurochemical Evaluation of Striatal Serotonergic Hyperinnervation in Rats Depleted of Dopamine at Infancy

Jackson

Abercrombie

1992

Journal of Neurochemistry

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Destruction of nigrostriatal dopamine (DA) neurons with 6-hydroxydopamine (6-OHDA) early in development results in hyperinnervation of striatum by the serotonergic afferents deriving from the dorsal raphe nucleus. We have used in vivo microdialysis to investigate the degree to which serotonergic neurotransmission in striatum is altered by this increase in the density of serotonin (5-HT) terminals. The effects of several manipulations known to influence 5-HT function on extracellular 5-HT and 5-hydroxyindoleacetic acid in striatum were compared in adult rats treated neonatally with 6-OHDA and in intact adult rats. Basal levels of 5-HT in extracellular fluid (ECF) of striatum were similar in neonatally DA-depleted rats and in intact rats. Perfusion with the 5-HT reuptake blocker, fluoxetine (100 microM), increased 5-HT in striatal ECF of neonatally DA-depleted rats to levels that were threefold greater than those achieved in intact rats. Likewise, K(+)-depolarization of the 5-HT terminals (100 mM in perfusate) or systemic administration of the 5-HT releaser, (+/-)-fenfluramine (10 mg/kg i.p.), increased the concentration of 5-HT in striatal ECF of neonatally DA-depleted rats to levels approximately threefold greater than those observed in striatum of intact rats. These findings indicate that the 5-HT hyperinnervation of striatum that takes place in rats depleted of DA at infancy is associated with an increased capacity for neurotransmitter release in this system. Concomitant increased in high-affinity 5-HT uptake may prevent the occurrence of any measurable changes in the resting concentration of 5-HT in striatal ECF.

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Model of brain serotonin metabolism. II. Physiological interpretation

Cited by 11 publications

References 0 publications

Monitoring the Effect of a Tryptophan Load on Brain Indole Metabolism in Freely Moving Rats by Simultaneous Cerebrospinal Fluid Sampling and Brain Dialysis

Monitoring the Effect of a Tryptophan Load on Brain Indole Metabolism in Freely Moving Rats by Simultaneous Cerebrospinal Fluid Sampling and Brain Dialysis

Targeted Delivery of Hormones to Tissues by Plasma Proteins

In Vivo Neurochemical Evaluation of Striatal Serotonergic Hyperinnervation in Rats Depleted of Dopamine at Infancy

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