The CSF HCO3− increase in hypercapnia relationship to HCO3−, glutamate, glutamine and NH3 in brain

Kazemi, Homayoun; Weyne, J; Leuven, Freddy Van; Leusen, I

doi:10.1016/0034-5687(76)90032-3

Cited by 24 publications

(11 citation statements)

References 32 publications

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“…Hypercapnic acidosis suppresses neuronal activity to minimize metabolic demand during DHCA. 27 Hypercapnia may be protective by reducing brain tissue glutamate concentrations 28 and/or brain tissue lactate 29 during ischemia. Hypercapnia decreases lactate production by inhibiting pyruvate dehydrogenase.…”

Section: Discussionmentioning

confidence: 99%

Comparison of neurologic outcome after deep hypothermic circulatory arrest with alpha-stat and pH-stat cardiopulmonary bypass in newborn pigs

Priestley

Golden

OʼHara

et al. 2001

The Journal of Thoracic and Cardiovascular Surgery

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Section: Discussionmentioning

confidence: 99%

Comparison of neurologic outcome after deep hypothermic circulatory arrest with alpha-stat and pH-stat cardiopulmonary bypass in newborn pigs

Priestley

Golden

OʼHara

et al. 2001

The Journal of Thoracic and Cardiovascular Surgery

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“…98 It has been reported that cerebral intraventricular administration of AAZ exterminates enhancement of [HCO 3 − ] CSF and interrupts pH of CSF during respiratory acidosis in experimental animals. 100,101 Parati et al found that systemic resting diastolic and mean arterial blood pressure was increased after 6 h and 2 days of advent at high altitude as compared with sea level. The CAI treatment (AAZ, 250 mg b.i.d) barred this enhancement, possibly due to lower sympathetic stimulation and elevated NO production.…”

Section: High Altitude Sicknessmentioning

confidence: 99%

Progress in the development of human carbonic anhydrase inhibitors and their pharmacological applications: Where are we today?

Mishra

Tiwari

Supuran

2020

Medicinal Research Reviews

190

166

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Carbonic anhydrases (CAs, EC 4.2.1.1) are widely distributed metalloenzymes in both prokaryotes and eukaryotes. They efficiently catalyze the reversible hydration of carbon dioxide to bicarbonate and H + ions and play a crucial role in regulating many physiological processes. CAs are wellstudied drug target for various disorders such as glaucoma, epilepsy, sleep apnea, and high altitude sickness. In the past decades, a large category of diverse families of CA inhibitors (CAIs) have been developed and many of them showed effective inhibition toward specific isoforms, and effectiveness in pathological conditions in preclinical and clinical settings. The discovery of isoform-selective CAIs in the last decade led to diminished side effects associated with off-target isoforms inhibition. The many new classes of such compounds will be discussed in the review, together with strategies for their development. Pharmacological advances of the newly emerged CAIs in diseases not usually associated with CA inhibition (neuropathic pain, arthritis, cerebral ischemia, and cancer) will also be discussed.

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“…However, can the fluctuations of HCO 3 − during hypercapnia be sufficient to change the activation of sAC in a functionally significant manner? sAC is most sensitive to bicarbonate ions in the low millimolar range (Chen et al 2000), whereas levels in CSF are usually ∼19 mM and rise by only 3 mM during extended periods of hypercapnia (Kazemi et al 1976), translating into a modest increase in sAC activity (Chen et al 2000). Whether this increase is functionally significant depends on sAC expression levels, cellular cAMP concentration and the extent to which this varies as a result of modulation of sAC by changing HCO 3 − concentrations.…”

Section: Modalities Of Chemosensing: Salient Stimulimentioning

confidence: 99%

“…sAC is most sensitive to bicarbonate ions in the low millimolar range (Chen et al . 2000), whereas levels in CSF are usually ∼19 m m and rise by only 3 m m during extended periods of hypercapnia (Kazemi et al . 1976), translating into a modest increase in sAC activity (Chen et al .…”

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confidence: 99%

Redefining the components of central CO₂ chemosensitivity – towards a better understanding of mechanism

Huckstepp

Dale

2011

The Journal of Physiology

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The field of CO2 chemosensitivity has developed considerably in recent years. There has been a mounting number of competing nuclei proposed as chemosensitive along with an ever increasing list of potential chemosensory transducing molecules. Is it really possible that all of these areas and candidate molecules are involved in the detection of chemosensory stimuli? How do we discriminate rigorously between molecules that are chemosensory transducers at the head of a physiological reflexversusthose that just happen to display sensitivity to a chemosensory stimulus? Equally, how do we differentiate between nuclei that have a primary chemosensory function, versusthose that are relays in the pathway? We have approached these questions by proposing rigorous definitions for the different components of the chemosensory reflex, going from the salient molecules and ions, through the components of transduction to the identity of chemosensitive cells and chemosensitive nuclei. Our definitions include practical and rigorous experimental tests that can be used to establish the identity of these components. We begin by describing the need for central CO2 chemosensitivity and the problems that the field has faced. By comparing chemosensory mechanisms to those in the visual system we suggest stricter definitions for the components of the chemosensory pathway. We then, considering these definitions, re-evaluate current knowledge of chemosensory transduction, and propose the ‘multiple salient signal hypothesis’ as a framework for understanding the multiplicity of transduction mechanisms and brain areas seemingly involved in chemosensitivity.

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The CSF HCO3− increase in hypercapnia relationship to HCO3−, glutamate, glutamine and NH3 in brain

Cited by 24 publications

References 32 publications

Comparison of neurologic outcome after deep hypothermic circulatory arrest with alpha-stat and pH-stat cardiopulmonary bypass in newborn pigs

Comparison of neurologic outcome after deep hypothermic circulatory arrest with alpha-stat and pH-stat cardiopulmonary bypass in newborn pigs

Progress in the development of human carbonic anhydrase inhibitors and their pharmacological applications: Where are we today?

Redefining the components of central CO₂ chemosensitivity – towards a better understanding of mechanism

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The CSF HCO3− increase in hypercapnia relationship to HCO3−, glutamate, glutamine and NH3 in brain

Cited by 24 publications

References 32 publications

Comparison of neurologic outcome after deep hypothermic circulatory arrest with alpha-stat and pH-stat cardiopulmonary bypass in newborn pigs

Comparison of neurologic outcome after deep hypothermic circulatory arrest with alpha-stat and pH-stat cardiopulmonary bypass in newborn pigs

Progress in the development of human carbonic anhydrase inhibitors and their pharmacological applications: Where are we today?

Redefining the components of central CO2 chemosensitivity – towards a better understanding of mechanism

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Product

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Redefining the components of central CO₂ chemosensitivity – towards a better understanding of mechanism