Transport of sulfate in the rabbit's brain

Hollingsworth, J. G.; Davson, Hugh

doi:10.1002/neu.480040407

Cited by 9 publications

(2 citation statements)

References 15 publications

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“…M6G enters the CSF more slowly than morphine with a CSF to plasma concentration ratio for M6G which slowly attained a value of 0.1 at 120 min. The observation that the brain ECF concentrations are higher than the CSF concentrations for both morphine and M6G confirm observations that have been made for a number of solutes (Hollingsworth & Davson, 1973). The AUC ECF to AUC CSF ratio was more elevated for M6G than for morphine (15 and 2, respectively) confirming that M6G was trapped in the brain ECF.…”

Section: Discussionsupporting

confidence: 89%

Elevated concentrations of morphine 6‐beta‐D‐glucuronide in brain extracellular fluid despite low blood–brain barrier permeability

Stain-Texier

Boschi

Sandouk

et al. 1999

British J Pharmacology

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1 This study was done to ®nd out how morphine 6-beta-D-glucuronide (M6G) induces more potent central analgesia than morphine, despite its poor blood ± brain barrier (BBB) permeability. The brain uptake and disposition of these compounds were investigated in plasma and in various brain compartments: extracellular¯uid (ECF), intracellular space (ICS) and cerebrospinal¯uid (CSF). 2 Morphine or M6G was given to rats at 10 mg kg 71 s.c. Transcortical microdialysis was used to assess their distributions in the brain ECF. Conventional tissue homogenization was used to determine the distribution in the cortex and whole brain. These two procedures were combined to estimate drug distribution in the brain ICS. The blood and CSF pharmacokinetics were also determined. 3 Plasma concentration data for M6G were much higher than those of morphine, with C max and AUC 4 ± 5 times more higher, T max shorter, and V Z f 71 (volume of distribution) and CL f 71 (clearance) 4 ± 6 times lower. The concentrations of the compounds in various brain compartments also di ered: AUC values for M6G were lower than those of morphine in tissue and CSF and higher in brain ECF. AUC values in brain show that morphine levels were four times higher in ICS than in ECF, whereas M6G levels were 125 higher in ECF than in ICS. 4 Morphine entered brain cells, whereas M6G was almost exclusively extracellular. This high extracellular concentration, coupled with extremely slow di usion into the CSF, indicates that M6G was predominantly trapped in the extracellular¯uid and therefore durably available to bind at opioid receptors.

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Section: Discussionsupporting

confidence: 89%

Elevated concentrations of morphine 6‐beta‐D‐glucuronide in brain extracellular fluid despite low blood–brain barrier permeability

Stain-Texier

Boschi

Sandouk

et al. 1999

British J Pharmacology

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“…I continued working at University College with my technician, Gillian Hollingworth (26), until I was due to retire at about age 66. Meanwhile the Fogarty Foundation had invited me to take a scholarship for a year after retiring, so I went to work at the NIH for a year.…”

Section: Illmentioning

confidence: 99%

Barriers and Fluids of the Eye and Brain

Segal¹

1992

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Ventriculo–cisternal perfusion of twelve amino acids in the rabbit

et al. 1982

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The clearances of twelve amino acids from the ventricles during ventriculo-cisternal perfusion in the rabbit have been measured; uptake by the brain was also measured and this permitted the separate computation of loss to brain and loss to blood during the perfusion. Clearance under carrier-free conditions was greater than when a concentration of 5mM unlabeled amino acid was present in the perfusion fluid. Brain uptake was also usually reduced by the presence of unlabeled amino acid due presumably to suppression of accumulation by brain cells. Reduction of transport across the blood-brain barrier would tend to increase brain uptake, and there was some evidence for a balance between the two opposing tendencies. Inhibition of clearance of a given labeled amino acid could be brought about by unlabeled amino acids of different molecular species. In general, the amino acids fell into three categories: neutral, acidic, and basic, and there was some overlap between them; of the neutral amino acids the A- and L-classification of Christensen was valid, although once again there was some overlap. If, during ventriculo-cisternal perfusion of a labeled amino acid, the activity of this labeled amino acid in the blood was raised well above that in the inflowing perfusion fluid, the labeled amino acid continued to be cleared from the perfusion fluid, suggesting uphill transport. On this basis it was suggested that the normally low concentrations of amino acids in the cerebrospinal fluid (CSF), by comparison with those in plasma, were due to an active transport from the CSF to the blood. Substrate-facilitated transport, whereby the penetration of labeled amino acid into the perfusion fluid from blood could be accelerated by adding unlabeled amino acid to the perfusion fluid, or vice versa, was demonstrated.

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Transport of sulfate in the rabbit's brain

Cited by 9 publications

References 15 publications

Elevated concentrations of morphine 6‐beta‐D‐glucuronide in brain extracellular fluid despite low blood–brain barrier permeability

Elevated concentrations of morphine 6‐beta‐D‐glucuronide in brain extracellular fluid despite low blood–brain barrier permeability

Barriers and Fluids of the Eye and Brain

Ventriculo–cisternal perfusion of twelve amino acids in the rabbit

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