The uptake and fate of the radiolabeled 5-hydroxytryptamine in isolated cerebral microvessels

Spatz, Maria; Maruki, Chikashi; Abe, Tomoko; Rausch, W. D.; Abe, Kazunori; Merkel, N.

doi:10.1016/0006-8993(81)90229-8

Cited by 26 publications

(11 citation statements)

References 6 publications

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“…The 5-HT released is expected to be inactivated by monoamine oxidase, which is expressed in brain endothelium (Kalaria and Harik, 1987;Brust et al, 1996b). Therefore, the presence of an endothelial plasma membrane transport system that is specific for 5-HT has been suggested (Spatz et al, 1981;Brust et al, 1995Brust et al, , 1996a. In previous studies, we have demonstrated that the tricyclic antidepressant [ 3 H]imipramine and the nontricyclic antidepressant [ 3 H]paroxetine bind specifically to microvessels of the porcine brain.…”

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confidence: 99%

Functional Expression of the Serotonin Transporter in Immortalized Rat Brain Microvessel Endothelial Cells

Brust

Friedrich

Krizbai

et al. 2000

Journal of Neurochemistry

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There is evidence from recent studies that the brain endothelium (of capillaries and/or larger vessels) may serve as a specific target for serotonin [5-hydroxytryptamine (5-HT)]. This neurotransmitter is expected to be involved in the regulation of the blood-brain barrier (BBB) permeability and/or of the cerebral blood flow via receptor-mediated mechanisms. Effective control of these processes depends on a speedy uptake and metabolism of released 5-HT molecules. To realize this, a similar mechanism of 5-HT uptake as in brain may exist at the BBB. In this study, we have demonstrated using RT-PCR that 5-HT transporter mRNA is present in the brain endothelium and that a saturable transport system for 5-HT is functionally expressed in immortalized rat brain endothelial cells (RBE4 cells). These cells take up [3H]5-HT by an active saturable process with a Km value of 397 +/- 64 nmol/L and a transport capacity of 51.7 +/- 3.5 pmol x g(-1) x min(-1). The 5-HT uptake depends on Na+, as indicated by the replacement of NaCl by LiCl. The 5-HT uptake was sensitive to specific 5-HT transport inhibitors such as paroxetine, clomipramine, fluoxetine, and citalopram but not to inhibitors of the vesicular amine transporter such as reserpine or tetrabenazine. Our results demonstrate that cerebral endothelial cells are able to participate actively in the removal and metabolism of the released 5-HT, which supports the concept of direct serotoninergic regulation of the BBB function.

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mentioning

confidence: 99%

Functional Expression of the Serotonin Transporter in Immortalized Rat Brain Microvessel Endothelial Cells

Brust

Friedrich

Krizbai

et al. 2000

Journal of Neurochemistry

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“…Capillary endothelia represent a third potentially important compartment for 5HT deaminiation because they are capable of 5HT uptake (Spatz et al, 1981), contain the MAO-A isoenzyme (Baranczyk-Kuzma et al, 1986;Riederer etal., 1989) and produce 5HIAA (Maruki etal., 1984). Reaction product for MAO was also observed in pineal capillaries (Juillard and Collin, 1979;MassonPevet and Pevet, 1989).…”

Section: Discussionmentioning

confidence: 99%

Sympathetic denervation and chronic serotonin uptake blockade by fluoxetine do not affect pineal gland 5-hydroxyindole acetic acid: evidence that oxidative deamination of pineal serotonin is a property of the pinealocyte

McNulty

Colin

1992

J. Neural Transmission

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This investigation tested the hypothesis that oxidative deamination of 5HT in the pineal gland occurs primarily in cellular compartments other than the pinealocyte (i.e., noradrenergic nerve terminals and glia). Following sympathetic denervation of the pineal gland by bilateral superior cervical sympathectomy, pineal levels of 5HT and its oxidative metabolite, 5HIAA, were measured by HPLC from samples collected at six time points over the 24 h photoperiod. The role of glia in 5HT deamination was further examined by chronic treatment with the 5HT uptake blocker, fluoxetine (10 mg/kg). Sympathectomy abolished the circadian rhythms of both 5HT and 5HIAA, but had no statistically significant effect on the ratio of 5HIAA/5HT compared to sham-operated and intact controls over the 24 h period. Pineal daytime levels of both 5HT and 5HIAA were unaffected by fluoxetine treatment. These findings indicate that the pinealocyte is an important cellular compartment for 5HT oxidative metabolism.

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“…Die zirkulierenden Monoamin-Vorstufen L-3, 4-Dihydroxyphenylalanin (L-Dopa) und L-5-Hydroxytryptophan, die mittels eines aktiven, energieabhängigen Aufnahmemechanismus leicht durch die vaskuläre Endothel- (1', 122,339). Die Aufnahme der Monoamine durch die Kapillaren erfolgt durch einen spezifischen, vermutlich an NA+-K'"ATPase gebundenen Vorgang, der unabhängil; ist vom L· und A-Transportsystem für Aminosäuren (1, 339); hingegen können die Hirngefäße die Metaboliten von NA und 5-HT (Nor-Metanephrin, Metanephrin, 5-HlES) nicht zurückhalten, sondern diese zeigen freie Diffusion (339). Unter pathologischen Bedingungen, wie Anoxie, Stoffwechselstörungen, Hypertonie u.a., kommt es zu Beeinträchtigung der Transportregulationsvorgänge fUr NT und ihrer Vorläufer durch Öffnung der BHS und Inaktivierung der kontrollierenden Enzymbarriere (1,122,240,254,339), die zu Störungen der zerebralen Durchblutung und der Mikrozirkulation führen.…”

Section: Zusammenfassungunclassified

Zentrale Neurotransmitter bei zerebraler Ischämie und Hirninfarkt

Jellinger¹,

Riederer²

1983

Fortschr Neurol Psychiatr

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Brain Neurotransmitters in CerebraI Ischemia and StrakeDisturbances of .biogenic amines and other putative neurotransmitters due to disorders of energY-depending synthesis, degradation and transport mechanism have been demonstrated in both experimental cerebraI ischemia and human brain infaretion. Their changes depend on the type, severity and duration of ischemia. Since neurotransmitters have variable effeets on cerebral vasculature, blood-brain barrier, (BBB), cerebraI blood flow and metabolism, their disorders may contribute to the development of postischemic brain damage and the complicating cerebraI edema.During short-term experimental cerebraI ischemia there are only minimal changes in cerebral biogenic amines, but despite improved cerebral energy metabolism significant alterations in catecholamine and indoleamine turnover and in the aetivity of degradating enzymes (MAO, COMT, etc.! occur in the postischemic reperfusion period, suggesting a "maturation phenomenon". Long-term cerebraI ischemia and cerebraI infarction are associated with severe depletion of dopamine, serotonin, with increased levels of their metabolites homovanillic acid and 5-hydroxy-indole acetic acid es weil as of GABA and cyclic AMP in both the necrotic area and the surrounding tissue. These changes are related to increased release, decreased synthesis, degradation and washout, and disorders of vascular amine transport due to reduced activity of related enzymes. Simultaneous increase of the 5-HT precursor tryptophan and its main metabolite kynurenine sUllllest decreased synthesis and turnover of 5-HT. Reduced activity of tyrosine hydroxylase and other degradating enzymes indicate reduced activities of catecholamine and serotonergic neuronal systems in postischemia. There is reduced synaptosomal uptake of DA, 5-HT and GABA with reduction in the number of aminergic receptor binding sites due to irreversible ischemic demage to synaptosomal membranes. Transient opening of the blood-brain barrier and increased amine transport from blood into brain tissue may promote postischemic disorders of microcirculation and edema. Bilateral changes in energy metabolism and decrease in monoamines seen after unilateral focal ischemia (in experimental models and human brain) are caused by remote effects of ischemia ("diaschisis") due to reduced cerebraI blood flow and edema. However, no bilateral effect of ischemia on the number of specific neuronal DA-and 5-HT binding sites and on DA uptake are evident which indicate a certain resistance of synaptosomal membranes towards ischemia.Th_ data and rather normal activity of cerebral tyrosine hydroxylase in metabolie encephalopathies (hepatic and diabetic coma) indicate a preferential oxygen supply to neuronal transmitter systems. Severe and long-Iasting ischemia, cerebral infarction with destruction of neurons and metabolie catastrophes (hepatic comal, however, induce a breakdown of energy-depending systems and are associated with disorders of the BBB. The perifocal edema zone surrounding recent infarction shows ...

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The uptake and fate of the radiolabeled 5-hydroxytryptamine in isolated cerebral microvessels

Cited by 26 publications

References 6 publications

Functional Expression of the Serotonin Transporter in Immortalized Rat Brain Microvessel Endothelial Cells

Functional Expression of the Serotonin Transporter in Immortalized Rat Brain Microvessel Endothelial Cells

Sympathetic denervation and chronic serotonin uptake blockade by fluoxetine do not affect pineal gland 5-hydroxyindole acetic acid: evidence that oxidative deamination of pineal serotonin is a property of the pinealocyte

Zentrale Neurotransmitter bei zerebraler Ischämie und Hirninfarkt

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