Decar☐ylase activity of the brain capillary walls and parenchyma in the rat, cat and monkey

Langelier, P.; Parent, André; Poirier, Louis

doi:10.1016/0006-8993(72)90495-7

Cited by 32 publications

(12 citation statements)

References 11 publications

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“…Mature female baboons (Papio papio) weighing [7][8][9][10][11][12][13] kg were obtained from Primate Imports Corp., Port Washington, Long Island, NY. They were trained over a period of 3 weeks to sit quietly, without tranquilizers, in a restraining chair.…”

Section: Methodsmentioning

confidence: 99%

[ ¹⁸ F]Fluoro-dopa, an analogue of dopa, and its use in direct external measurements of storage, degradation, and turnover of intracerebral dopamine

Garnett

Firnau

Chan

et al. 1978

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

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3,4-Dihydroxy-5-fluorophenylalanine, fluorodopa, was injected into rats in which unilateral lesions of the nigrostriatal pathway had been made. The rats rotated towards the side with the lesions, thus providing further evidence that fluoro-dopa is an analogue of dopa. ['8F]Fluoro-dopa was then injected intravenously into fully conscious baboons. A wellcollimated scintillation detector, aligned along the occipitomental axis, recorded the accumulation of 18F in the brain. prevented the accumulation of 18F; reserpine, known to release stored intracerebral dopamine, discharged 18F; pargyline, a monoamine oxidase inhibitor, and haloperidol, a Known augmentor of intracerebral dopamine turnover, increased the rate of accumulation of 18F. These changes in the accumulation of intracerebral 18F, after were commensurate with the known action of the drugs used to induce them and demonstrate the use of a y-emitting precursor of a neurotransmitter to monitor simply, atraumatically, and externally the intracerebral metabolism of the transmitter in fully conscious primates. When applied to man, the same technique shouldbe able to provide more conclusive evidence than is presently available for the role of catecholamines in schizophrenia and depression. It should also provide further insight into the natural history of nigrostriatal diseases and the action of drugs used in their treatment. There is no direct atraumatic method by which the localization or metabolism of intracerebral neurotransmitters can be measured during life in man. However, if a neurotransmitter were labeled with a Ry-emitting radionuclide it would be possible, using standard nuclear medicine techniques, to define both the intracerebral distribution and the regional rate of turnover of the molecule. Few of the neurotransmitters cross the bloodbrain barrier and, further, the half-lives of the Ry-emitting isotopes of their constituent atoms are too short to be used readily. MATERIALS AND METHODSResponse of Rats with Unilateral Lesions in the Substantia Nigra to Fluoro-dopa. Unilateral lesions of the substantia nigra of male Sprague-Dawley rats, 250-300 g, were made with 6-hydroxy-dopamine according to the method of Ungerstedt (5). After recovery each rat was treated with carbidopa (100 mg/kg of body weight) and placed in a round glass jar, 30-cm diameter. The rate at which the rats circled in the jar was recorded visually during a control period, after DL-dopa (100 mg/kg), and after apomorphine (10 mg/kg). Only rats that circled in response to both DL-dopa and apomorphine were used in subsequent experiments. These rats were then given intraperitoneally fluoro-dopa, 230 mg/kg, dissolved in saline with 1% ascorbic acid, and the rate at which each rat rotated was recorded for 1 hr after it had begun to circle. The dose of fluoro-dopa was chosen to be equivalent to 100 mg of dopa per kg on the assumption that at physiological pH approximately half of the fluoro-dopamine derived from fluoro-dopa would be un-ionized whereas almost all of the dopamine ma...

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Section: Methodsmentioning

confidence: 99%

[ ¹⁸ F]Fluoro-dopa, an analogue of dopa, and its use in direct external measurements of storage, degradation, and turnover of intracerebral dopamine

Garnett

Firnau

Chan

et al. 1978

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

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“…Therefore, provided the precursor (DOPA) is presented beyond the TH regulatory point, the striatum, minus its dopaminergic nerves, can still synthesize and metabolize dopamine as efficiently as an intact striatum. The decarboxylase enzyme, however, is known to be present in both nonneural (glia, endothelium) and other monoaminergic neurones (Langelier et al, 1972;Jaeger et al, 1973;Hefti et al, 1981;Commissiong, 1985b;El Gemayel et al, 1986). Thus considerable caution should be exercised in the interpretation of dopamine metabolism data, since it is likely that a large fraction of DOPAC and HVA may be non-neural in origin, and therefore may not be indicative of events in the dopaminergic neurone.…”

Section: Electical Stimulationmentioning

confidence: 99%

Regulation of the synthesis and metabolism of striatal dopamine after disruption of nerve conduction in the medial forebrain bundle

Commissiong

Slimovitch

Toffano

1990

British J Pharmacology

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1 After physical (knife-cut) or chemically-mediated (tetrodotoxin 300nm, 1.5p1; 1.Oplmin-1) interruption of nerve conduction in the nigrostriatal tract, there was a marked increase in the synthesis and metabolism of dopamine in the isolated dopaminergic nerve terminals of the striatum. The effect peaked at 4h post-transection, at which time 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) were increased by 300% and 700% respectively (DOPAC: 27+13 vs 80+17nmolg-1; HVA: 6.66+3.57 vs 54+18nmolg 1). The increases in dopamine content and metabolism are secondary to an increase in the rate of synthesis on the lesioned side, versus the intact, control side. 2 In both experimental situations, haloperidol (1.0mgkg-1, i.p.) retained its known ability to induce a significant increase in DOPAC and HVA in the striatum, despite the interruption of nerve conduction in the nigrostriatal tract. 3 Six days after cutting the left nigrostriatal tract, dopamine in the left striatum was reduced to < 5% of the control value, and DOPAC and HVA were not detectable. In the denervated, left striatum, the synthesis of dopamine (from injected L-DOPA), and its metabolism to DOPAC and HVA, occurred to the same degree as in the intact right side. In these DOPA-treated rats, haloperidol (1.Omgkg-1, i.p.) caused a further increase in DOPAC and HVA in the intact striatum, but not in the denervated striatum. 4 Under non-stressful conditions, using a combination of anaesthetic treatments, electrical stimulation (400 yA, 0.4 ins, 15 Hz, 15 min) of the nigrostriatal tract did not increase DOPAC or HVA in the striatum on the stimulated side.5 It is concluded (a) that there is a significant presynaptic, and/or local circuit mechanism capable of activating the synthesis and metabolism of dopamine in the isolated, striatal, dopaminergic nerve terminals. Furthermore, haloperidol can act directly on the striatal, dopaminergic nerve terminal, to cause an increase in the synthesis and metabolism of striatal dopamine. (b) After degeneration of the striatal dopaminergic nerves, the denervated striatum retains the ability to synthesize (from L-DOPA) and metabolize dopamine, to the same degree as the intact, innervated, contralateral striatum. (c) When stress is minimized, and release of dopamine is induced by electrical stimulation of the medial forebrain bundle, the catabolism of dopamine (to DOPAC and HVA) during the release-uptake cycle may not be a significant factor under physiological conditions. (d) When dopamine synthesis is increased in the striatum, the normal blood concentration of tyrosine is adequate to sustain the increased synthesis, and precursor availability is not a limiting factor. (e) These results suggest that some of the basic concepts about the neurochemical/neurophysiological regulation of monoaminergic neurones may require further reevaluation.

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“…When the endothelial decarboxylase in inhibited, ¿-dopa can pass freely in brain parenchyma where it is transformed into dopa mine. Direct evidence in favour of this mechanism is lacking, and the problem is further complicated by the fact that fluorescence of brain capillary walls, after peripheral loading with ¿-dopa, is not a general phenomenon among species; it is not found in the cat, monkey (Langelier et al, 1972), rabbit, or guinea pig (Constantinidis, unpublished data).…”

Section: Introductionmentioning

confidence: 99%

Effect of Peripheral Decarboxylase Inhibition on HVA and 5HIAA in Cerebrospinal Fluid of Depressed Patients

Gaillard¹,

Constantinidis²,

Tissot³

1975

Neuropsychobiology

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The effects of benserazide on the level of homovanillic acid and 5-hydroxy-indoleacetic acid in CSF have been investigated in 1 manic and 11 depressed patients. Benserazide induced no change on both metabolites. This negative result supports the view that monoamine metabolites in CSF, in the absence of loading with an exogenous precursor, originate mostly from brain parenchyma, without significant contribution of the metabolism in capillary walls.

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Decar☐ylase activity of the brain capillary walls and parenchyma in the rat, cat and monkey

Cited by 32 publications

References 11 publications

[ ¹⁸ F]Fluoro-dopa, an analogue of dopa, and its use in direct external measurements of storage, degradation, and turnover of intracerebral dopamine

[ ¹⁸ F]Fluoro-dopa, an analogue of dopa, and its use in direct external measurements of storage, degradation, and turnover of intracerebral dopamine

Regulation of the synthesis and metabolism of striatal dopamine after disruption of nerve conduction in the medial forebrain bundle

Effect of Peripheral Decarboxylase Inhibition on HVA and 5HIAA in Cerebrospinal Fluid of Depressed Patients

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Decar☐ylase activity of the brain capillary walls and parenchyma in the rat, cat and monkey

Cited by 32 publications

References 11 publications

[ 18 F]Fluoro-dopa, an analogue of dopa, and its use in direct external measurements of storage, degradation, and turnover of intracerebral dopamine

[ 18 F]Fluoro-dopa, an analogue of dopa, and its use in direct external measurements of storage, degradation, and turnover of intracerebral dopamine

Regulation of the synthesis and metabolism of striatal dopamine after disruption of nerve conduction in the medial forebrain bundle

Effect of Peripheral Decarboxylase Inhibition on HVA and 5HIAA in Cerebrospinal Fluid of Depressed Patients

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[ ¹⁸ F]Fluoro-dopa, an analogue of dopa, and its use in direct external measurements of storage, degradation, and turnover of intracerebral dopamine

[ ¹⁸ F]Fluoro-dopa, an analogue of dopa, and its use in direct external measurements of storage, degradation, and turnover of intracerebral dopamine