Cl-HCO3 exchange in choroid plexus: analysis by the DMO method for cell pH

1985 ◽  
Vol 249 (4) ◽  
pp. F478-F484 ◽  
Author(s):  
C. E. Johanson ◽  
Z. Parandoosh ◽  
Q. R. Smith
Keyword(s):  
Cerebrospinal Fluid ◽  
Steady State ◽  
Choroid Plexus ◽  
Equilibrium Distribution ◽  
Disulfonic Acid ◽  
Adult Rat ◽  
Extracellular Acidosis ◽  
Anion Distribution ◽  
Electrochemical Equilibrium

[14C]DMO distribution was used to measure steady-state intracellular pH (pHi) and [HCO3]i in adult rat choroid plexus (CP) incubated in synthetic cerebrospinal fluid (CSF) for 30 min. In controls at 37 degrees C, mean pHi (6.95 at PCO2 = 30 mmHg) was close to corresponding in vivo values; and [HCO3]i/[HCO3]csf, i.e., rHCO3, was 0.37. At normal [HCO3]csf = 18 mM, cell HCO3 was accumulated threefold above electrochemical equilibrium (as estimated from Em = -50 mV). [HCO3]i decreased proportionally with [HCO3]csf, as the latter was altered from 47 to 9 mM; in severe extracellular acidosis [( HCO3]csf = 3.7 mM), [HCO3]i was not reduced further and so rHCO3 rose to 0.66. Except in low [HCO3]csf, acetazolamide and ouabain (10(-4) M) caused small depletion of cell HCO3. 4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic acid lowered [HCO3]i by 60%, thus decreasing rHCO3 (0.16) and rCl (0.25) to values close to estimated equilibrium distribution (0.15). Substitution of CSF Cl with isethionate resulted in marked alkalinization of pHi when [Cl]csf was depleted to 12 mM. Augmented PCO2 associated with temperature reduction to 15 degrees C elevated [HCO3]i, thereby increasing rHCO3 (to 0.66) as well as rCl. Anion distribution ratios indicate heteroanion exchange in mammalian CP.

scholarly journals Modulation of the cost of pHi regulation during metabolic depression: a (31)P-NMR study in invertebrate (Sipunculus nudus) isolated muscle

2000 ◽  
Vol 203 (16) ◽  
pp. 2417-2428 ◽  
Author(s):  
H.O. Portner ◽  
C. Bock ◽  
A. Reipschlager
Keyword(s):  
Steady State ◽  
Marine Invertebrate ◽  
Metabolic Depression ◽  
Acid Base ◽  
Extracellular Acidosis ◽  
Nmr Study ◽  
Sipunculus Nudus ◽  
Delayed Recovery ◽  
Dimethyl Amiloride

Extracellular acidosis has been demonstrated to play a key role in the process of metabolic depression under long-term environmental stress, exemplified in the marine invertebrate Sipunculus nudus. These findings led to the hypothesis that acid-base regulation is associated with a visible cost depending on the rate and mode of H(+)-equivalent ion exchange. To test this hypothesis, the effects of different ion-transport inhibitors on the rate of pH recovery during hypercapnia, on energy turnover and on steady-state acid-base variables were studied in isolated body wall musculature of the marine worm Sipunculus nudus under control conditions (pHe 7.90) and during steady-state extracellular acidosis (pHe 7.50 or 7.20) by in vivo (31)P-NMR and oxygen consumption analyses. During acute hypercapnia (2 % CO(2)), recovery of pHi was delayed at pHe 7.5 compared with pHe 7.9. Inhibition of the Na(+)/H(+)-exchanger by 5-(N,N-dimethyl)-amiloride (DMA) at pHe 7.5 delayed recovery even further. This effect was much smaller at pHe 7.9. Inhibition of anion exchange by the addition of the transport inhibitor 4, 4′-diisothiocyanatostilbene-2,2′-disulphonic acid (DIDS) prevented pH recovery at pHe 7.5 and delayed recovery at pHe 7.9, in accordance with an effect on Na(+)-dependent Cl(−)/HCO(3)(−) exchange. The effects of ouabain, DIDS and DMA on metabolic rate were reduced at low pHe, thereby supporting the conclusion that acidosis caused the ATP demand of Na(+)/K(+)-ATPase to fall. This reduction occurred via an inhibiting effect on both Na(+)/H(+)- and Na(+)-dependent Cl(−)/HCO(3)(−) (i.e. Na(+)/H(+)/Cl(−)/HCO(3)(−)) exchange in accordance with a reduction in the ATP demand for acid-base regulation during metabolic depression. Considering the ATP stoichiometries of the two exchangers, metabolic depression may be supported by the predominant use of Na(+)/H(+)/Cl(−)/HCO(3)(−) exchange under conditions of extracellular acidosis.

Myo-inositol transport in the central nervous system

1975 ◽  
Vol 228 (5) ◽  
pp. 1510-1518 ◽  
Author(s):  
R Spector ◽  
AV Lorenzo
Keyword(s):  
Central Nervous System ◽  
Cerebrospinal Fluid ◽  
Nervous System ◽  
Choroid Plexus ◽  
Intraventricular Injection ◽  
Affinity Constant ◽  
Rapid Injection ◽  
The Central Nervous System

Free myo-inositol (inositol) transport into the cerebrospinal fluid (CSF), brain, and choroid plexus and out of the cerebrospinal fluid was measured in rabbits. In vivo, inositol transport from blood into choroid plexus, CSF, and brain was saturable with an apparent affinity constant (K-t) of approximately 0.1 mM. The relative turnover of free inositol in choroid plexus (16 percent/h) was higher than in CSF 4percent/h) and brain (0.3percent/h) when meausred by tissue penetration of tracer [3-H]-labeled inositol injected into blood. However, the passage of tracer inositol was not greater than the passage of mannitol into brain when measured 15 s after a rapid injection of inositol and mannitol into the left common carotid artery. From the CSF, the clearance of inositol relative to inulin was saturable after the intraventricular injection of various concentrations of inositol and inulin. Moreover, a portion of the inositol cleared from the CSF entered brain by a saturable mechanism. In vitro, choroid plexuses, isolated from rabbits and incubated in artificial CSF, accumulated [3-H-labeled myo-inositol against a concentration gradient by a specific, active, saturable process with a K-t of 0.2 mM inositol. These results were interpreted as showing that the entry of inositol into the central nervous system from blood is regulated by a saturable transport system, and that the locus of this system may be, in part, in the choroid plexus.

Active transport of chloride by lateral ventricle choroid plexus of the rat

1985 ◽  
Vol 249 (4) ◽  
pp. F470-F477 ◽  
Author(s):  
Q. R. Smith ◽  
C. E. Johanson
Keyword(s):  
Cerebrospinal Fluid ◽  
Choroid Plexus ◽  
Active Transport ◽  
Lateral Ventricle ◽  
Bath Temperature ◽  
Methyl Sulfate ◽  
Choroid Plexus Epithelium ◽  
Adult Rat ◽  
Cation Substitutions ◽  
K Transport

The nature of Cl transport and its relation to Na and K transport were analyzed in adult rat lateral ventricle choroid plexus incubated in cerebrospinal fluid (CSF) medium at 37 degrees C and PCO2 = 30 mmHg. In synthetic CSF (extracellular Cl [( Cl]o) = 130 mM), the intracellular Cl [( Cl]i) was three times that estimated for passive distribution. Choroid plexus [Cl]i was not determined by Donnan distribution because [Cl]i remained constant at approximately 50 mM while the [K]i/[K]o ratio was varied 10-fold by drugs and cation substitutions. A [Cl]i/[Cl]o ratio of approximately 0.38 was found when [Cl]o was varied from 15 to 130 mM by isosmotic replacement of Cl with methyl sulfate or isethionate. However, the [Cl]i/[Cl]o ratio increased to greater than 1.0 when [Cl]o was lowered below 5 mM. Reduction in bath temperature to 15 degrees C (CSF PCO2 = 50 mmHg) increased both [Cl]i/[Cl]o and [HCO3]i/[HCO3]o to approximately 0.6. SITS, an inhibitor of Cl-HCO3 transport, reduced [Cl]i by 18 mM, decreasing the [Cl]i/[Cl]o ratio close to the equilibrium value. In contrast, neither furosemide (10(-3) M) nor low CSF [Na]o (3 mM) reduced Cl accumulation. It is concluded that uphill movement of Cl into choroid plexus epithelium occurs primarily by Cl-HCO3 antiport and not by Na-Cl symport.

Cisterna magna microdialysis of 22Na to evaluate ion transport and cerebrospinal fluid dynamics

1991 ◽  
Vol 74 (6) ◽  
pp. 965-971 ◽  
Author(s):  
Neville W. Knuckey ◽  
Angela G. Fowler ◽  
Conrad E. Johanson ◽  
James R. B. Nashold ◽  
Mel H. Epstein
Keyword(s):  
Cerebrospinal Fluid ◽  
Ion Transport ◽  
Choroid Plexus ◽  
Systemic Circulation ◽  
Content Type ◽  
Cisterna Magna ◽  
Control Versus ◽  
The Central Nervous System ◽  
Na Uptake

✓ Microdialysis is used in vivo for measuring compounds in brain interstitial fluid. The authors describe another application of this technique to the central nervous system, namely microprobe dialysis in the cisterna magna to study the dynamics of ion transport and cerebrospinal fluid (CSF) formation in the rat. The choroid plexus is the major source of CSF, which is produced by active transport of Na from blood into the cerebral ventricles. Formation of CSF is directly proportional to the blood-to-CSF transport of Na. By injecting 22Na into the systemic circulation and quantifying its movement into CSF by microdialysis, one can reliably estimate alterations in the rate of CSF formation. The sensitivity of this system was determined by administering acetazolamide, a standard inhibitor of CSF production. Because acetazolamide is known to decrease CSF formation by 40% to 50%, the cisternal microdialysis system in animals treated with this drug should detect a corresponding decrease in the amount of 22Na dialyzed. This hypothesis is supported by the 22Na uptake curves for control versus treated animals: that is, by the acetazolamide-induced average diminution of about 45% in both the rate and extent of tracer accession to dialysate. Bumetanide, a loop diuretic, reduced by 30% the 22Na entry into dialysate. Microprobe dialysis of fluid in the cisterna magna is thus a minimally invasive and economical method for evaluating effects of drugs and hormones on the choroid plexus-CSF system.

GAS1 is present in the cerebrospinal fluid and is expressed in the choroid plexus of the adult rat

2016 ◽  
Vol 146 (3) ◽  
pp. 325-336 ◽  
Author(s):  
Alberto E. Ayala-Sarmiento ◽  
Enrique Estudillo ◽  
Gilberto Pérez-Sánchez ◽  
Arturo Sierra-Sánchez ◽  
Lorenza González-Mariscal ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Choroid Plexus ◽  
Adult Rat

Cotransport of sodium and chloride by the adult mammalian choroid plexus

1990 ◽  
Vol 258 (2) ◽  
pp. C211-C216 ◽  
Author(s):  
C. E. Johanson ◽  
S. M. Sweeney ◽  
J. T. Parmelee ◽  
M. H. Epstein
Keyword(s):  
Cerebrospinal Fluid ◽  
Choroid Plexus ◽  
Drug Effects ◽  
Disulfonic Acid ◽  
Base Line ◽  
Sprague Dawley ◽  
Disulfonic Stilbene ◽  
Fluid Formation ◽  
Vitro Analysis

Cerebrospinal fluid formation stems primarily from the transport of Na and Cl in choroid plexus (CP). To characterize properties and modulation of choroidal transporters, we tested diuretics and other agents for ability to alter ion transport in vitro. Adult Sprague-Dawley rats were the source of CPs preincubated with drug for 20 min and then transferred to cerebrospinal fluid (CSF) medium containing 22Na or 36Cl with [3H]mannitol (extracellular correction). Complete base-line curves were established for cellular uptake of Na and Cl at 37 degrees C. The half-maximal uptake occurred at 12 s, so it was used to assess drug effects on rate of transport (nmol Na or Cl/mg CP). Bumetanide (10(-5) and 10(-4) M) decreased uptake of Na and Cl with maximal inhibition (up to 45%) at 10(-5) M. Another cotransport inhibitor, furosemide (10(-4) M), reduced transport of Na by 25% and Cl by 33%. However, acetazolamide (10(-4) M) and atriopeptin III (10(-7) M) significantly lowered uptake of Na (but not Cl), suggesting effect(s) other than on cotransport. The disulfonic stilbene 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS; 10(-4) M), known to inhibit Cl-HCO3 exchange, substantially reduced the transport of 36Cl. Bumetanide plus DIDS (both 10(-4) M) caused additive inhibition of 90% of Cl uptake, which provides strong evidence for the existence of both cotransport and antiport Cl carriers. Overall, this in vitro analysis, uncomplicated by variables of blood flow and neural tone, indicates the presence in rat CP of the cotransport of Na and Cl in addition to the established Na-H and Cl-HCO3 exchangers.

scholarly journals Kinetic Profile of the Transcriptome Changes Induced in the Choroid Plexus by Peripheral Inflammation

2009 ◽  
Vol 29 (5) ◽  
pp. 921-932 ◽  
Author(s):  
Fernanda Marques ◽  
João C Sousa ◽  
Giovanni Coppola ◽  
Ana M Falcao ◽  
Ana João Rodrigues ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Choroid Plexus ◽  
Acute Phase ◽  
Acute Phase Proteins ◽  
Brain Parenchyma ◽  
Matrix Remodeling ◽  
Choroid Plexus Epithelial Cell ◽  
Blood Concentrations ◽  
The Brain

The choroid plexus, being part of the blood-brain barriers and responsible for the production of cerebrospinal fluid, is ideally positioned to transmit signals into and out of the brain. This study, using microarray analysis, shows that the mouse choroid plexus displays an acute-phase response after an inflammatory stimulus induced in the periphery by lipopolysaccharide (LPS). Remarkably, the response is specific to a restricted number of genes (out of a total of 24,000 genes analyzed, 252 are up-regulated and 173 are down-regulated) and transient, as it returns to basal conditions within 72 h. The up-regulated genes cluster into families implicated in immune-mediated cascades and in extracellular matrix remodeling, whereas those down-regulated participate in maintenance of the barrier function. Importantly, several acute-phase proteins, whose blood concentrations rise in response to inflammation, may contribute to the effects observed in vivo after LPS injection, as suggested by the differential response of primary choroid plexus epithelial cell cultures to LPS alone or to serum collected from animals exposed to LPS. By modulating the composition of the cerebrospinal fluid, which will ultimately influence the brain parenchyma, the choroid plexus response to inflammation may be of relevance in brain homeostasis in health and disease.

scholarly journals Glucocorticoids reset circadian clock in choroid plexus via period genes

2020 ◽  
Author(s):  
Karolína Liška ◽  
Martin Sládek ◽  
Vendula Čečmanová ◽  
Alena Sumová
Keyword(s):  
Cerebrospinal Fluid ◽  
Choroid Plexus ◽  
Glucocorticoid Receptors ◽  
Clock Gene ◽  
Time Of Day ◽  
The Body ◽  
Surgical Removal ◽  
The Brain

The epithelial cells of choroid plexus (CP) in brain ventricles produce cerebrospinal fluid and act as the blood-cerebrospinal fluid barrier. In this study, we confirmed that CP in the 4th ventricle is composed of cellular oscillators that all harbor glucocorticoid receptors and are mutually synchronized to produce a robust clock gene expression rhythm detectable at the tissue level in vivo and in vitro. Animals lacking glucocorticoids (GCs) due to surgical removal of adrenal glands had Per1, Per2, Nr1d1 and Bmal1 clock gene rhythmicity in their CP significantly dampened, whereas subjecting them to daily bouts of synthetic GC analog, dexamethasone (DEX), reinforced those rhythms. We verified these in vivo effects using an in vitro model of organotypic CP explants; depending on time of its application, DEX significantly increased the amplitude and efficiently reset the phase of the CP clock. The results are the first description of a PRC for a non-neuronal clock in the brain, demonstrating that CP clock shares some properties with the non-neuronal clocks elsewhere in the body. Finally, we found that DEX exhibited multiple synergic effects on the CP clock, including acute activation of Per1 expression and change of PER2 protein turnover rate. The DEX-induced shifts of the CP clock were partially mediated via PKA-ERK1/2 pathway. The results provide first evidence that the GC rhythm strengthens and entrains the clock in the CP helping thus fine-tune the brain environment according to time of day.

Pantothenic acid transport and metabolism in the central nervous system

1986 ◽  
Vol 250 (2) ◽  
pp. R292-R297 ◽  
Author(s):  
R. Spector
Keyword(s):  
Central Nervous System ◽  
Cerebrospinal Fluid ◽  
Choroid Plexus ◽  
Pantothenic Acid ◽  
Transport Systems ◽  
Intraventricular Injection ◽  
Acid Transport ◽  
Constant Rate ◽  
The Central Nervous System

The mechanisms by which pantothenic acid (PA) enters and leaves brain, choroid plexus, and cerebrospinal fluid (CSF) were investigated by injecting [3H]PA either intravenously or intraventricularly into adult rabbits. [3H]PA, either alone or together with unlabeled PA, was infused at a constant rate into conscious rabbits. At 180 min, [3H]PA readily entered CSF, choroid plexus, and brain. In brain, CSF, and plasma, greater than 90% of the 3H was associated with [3H]PA. The addition of 200 mumol/kg PA to the infusion syringe decreased the penetration of [3H]PA into brain and CSF by approximately 70%. Two hours after the intraventricular injection of [3H]PA, [3H]PA was rapidly cleared from the CSF by a probenecid-sensitive mechanism. No metabolism of the [3H]PA occurred in brain. However, 18 h after the intraventricular injection of 37 microCi (34 nmol) of [3H]PA, approximately 40% of the 3H remaining in forebrain was converted to [3H]CoA. These results show that PA enters and leaves CSF and brain by saturable transport systems. However, [3H]PA is very slowly converted to [3H]CoA in brain in vivo.

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