Specificity of ascorbic acid transport system of the central nervous system

Spector, Reynold; Lorenzo, AV

doi:10.1152/ajplegacy.1974.226.6.1468

Cited by 87 publications

(37 citation statements)

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“…Subsequent in vivo studies carried out by us and others confirmed the remarkable homeostasis of AA in brain and CSF in rabbits using ( 14 C)AA [4,36,37]. The fact that the CP transport system is normally one-half saturated with AA in vivo allows effective homeostasis.…”

Section: Vitamin C (Ascorbic Acid; Aa)mentioning

confidence: 76%

“…The system is very specific in that isoascorbic acid has only one tenth the affinity for the CP AA transport system in vitro and in vivo, although iso AA has the same affinity as AA for the enzyme dopamine hydrolase (isolated from brain) [37].…”

Section: Vitamin C (Ascorbic Acid; Aa)mentioning

confidence: 99%

“…The transport system in CP is similar to the AA reabsorption system in renal tubules with a Kt F0.05 mmol/l also. Teleologically, the brain requires stable concentrations of AA for proper functioning; the systems in gut, kidney, CP and possibly the BBB all work in concert to provide stable AA levels in the CSF and ECS of brain [2,4,36,37]. Developmentally the system is fully operational at birth [40].…”

Section: Vitamin C (Ascorbic Acid; Aa)mentioning

confidence: 99%

“…It is still not completely clear how much AA enters brain via the CP-CSF route versus directly via brain capillaries. Hammerstrom, and Spector and colleagues [4,16,37,38] suggest that greater than 50% of AA in brain enters via CP-CSF route, whereas Lam and Daniel [39] conclude that the CP-CSF route supplies only 10-20%. However, Lam and Daniel's hypothesis does not explain the autoradiographic data and the in vivo tissue (analytical) data which show initial entry into brain from brain surfaces closest to CSF [16,[36][37][38].…”

Section: Vitamin C (Ascorbic Acid; Aa)mentioning

confidence: 99%

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Drug Transport in the Mammalian Central Nervous System: Multiple Complex Systems

Spector¹

2000

Pharmacology

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The rate of entry into and distribution of drugs and endogenous substances within the mammalian central nervous system (CNS) depend on the peculiar anatomy of the blood-brain and blood-cerebrospinal fluid barriers, the physicochemical nature of the substance or drug, and in many cases, multiple, complex specialized carriers. This review summarizes a systemic methodological and integrative approach to understanding the pharmacokinetic behavior of many drugs in the CNS in the context of the CNS barrier systems, focusing on recent data, several broad principles and selected examples. Standards of proof for valid conclusions are emphasized.

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Section: Vitamin C (Ascorbic Acid; Aa)mentioning

confidence: 76%

Section: Vitamin C (Ascorbic Acid; Aa)mentioning

confidence: 99%

Section: Vitamin C (Ascorbic Acid; Aa)mentioning

confidence: 99%

Section: Vitamin C (Ascorbic Acid; Aa)mentioning

confidence: 99%

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Drug Transport in the Mammalian Central Nervous System: Multiple Complex Systems

Spector¹

2000

Pharmacology

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“…However, the physiological function of ascorbic acid in the brain is unknown. Spector and Lorenzo (24,25) reported that L ascorbic acid appeared to be transported from the plasma to the brain via cerebrospinal fluid by a carrier mediated, energy-dependent and stereospecific system. Furthermore, intravenous administration of dehydro-ascorbic acid stimulated the central nervous system (26) and the decreased respiration of the cerebral cortex seen after administration of pento barbitone was restored by ascorbic acid (27).…”

Section: ) Purification Of the Factormentioning

confidence: 99%

Ascorbic acid, an endogenous factor required for acetylcholine release from the synaptic vesicles.

Kuo

Yoshida

1980

Jpn.J.Pharmacol

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Abstract-TheACh-releasing factor, which is required for ACh release in presence of 2 mM ATP, 2 mM Mg and 10-5 M Ca from isolated synaptic vesicles, was purified from the synaptosomal cytoplasm of rat brain by Sephadex G-15, DEAE-Sephadex, Sephadex G-10 and AG50W-2X column chromatographies and identified as ascorbic acid. A low concentration of L-ascorbic acid (5 x 10-6 M) produced a release of ACh from the vesicles in the presence of ATP, MgCl2 and CaC12, as did synaptosomal cytoplasm. This release of ACh induced by L-ascorbic acid was found to be dissociable from formation of lipid peroxide. These findings are discussed in relation to the physiological role of L-ascorbic acid in the brain.It is generally accepted that Ca ion is important in the process of transmitter release (1). Injection of Ca++ into the nerve terminals produced a release of acetylcholine (ACh), as reported by Miledi (2). Under physiological conditions, arrival of an action potential at the nerve terminal causes an influx of Ca++ due to conformational changes of synaptic plasma membranes and this consequent rise in intracellular Ca++ concentration induces a release of transmitter(s). However, the role of intracellular Ca++ in the process of transmitter release is unknown.Although recent studies have indicated that ACh is released from both cytoplasm and synaptic vesicles (3), participation of the synaptic vesicles in ACh release induced by stimu lation is supported by the Quantal theory (4) and results of histological studies (5). Ac cordingly, one site of action of Ca++ in the nerve terminals is considered to be the synaptic vesicles, the ACh storing granules.We isolated synaptic vesicles from rat brain and examined the Ca++ dependent response.We found that a low concentration of Ca++ (10-s M to 10-5 M) significantly enhanced ACh release from the synaptic vesicles on addition of synaptosomal cytoplasm (sap) in the presence of ATP and Mg++ (6, 7).On the basis of this finding, we attempted to purify the factor required for ACh release from the vesicles in order to elucidate the mechanism of transmitter release from presynaptic nerve terminals.

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High Plasma Ascorbic Acid Levels in Premature Neonates With Intraventricular Hemorrhage

Arad¹

1983

Arch Pediatr Adolesc Med

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Specificity of ascorbic acid transport system of the central nervous system

Cited by 87 publications

References 0 publications

Drug Transport in the Mammalian Central Nervous System: Multiple Complex Systems

Drug Transport in the Mammalian Central Nervous System: Multiple Complex Systems

Ascorbic acid, an endogenous factor required for acetylcholine release from the synaptic vesicles.

High Plasma Ascorbic Acid Levels in Premature Neonates With Intraventricular Hemorrhage

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