scholarly journals Carbonic anhydrase inhibitors modify intracellular pH transients and contractions of rat middle cerebral arteries during CO2/HCO3– fluctuations

2017 ◽  
Vol 38 (3) ◽  
pp. 492-505 ◽  
Author(s):  
Jacob K Rasmussen ◽  
Ebbe Boedtkjer
Keyword(s):  
Carbonic Anhydrase ◽  
Intracellular Ph ◽  
Cerebral Arteries ◽  
Carbonic Anhydrase Activity ◽  
Carbonic Anhydrases ◽  
Intracellular Acidification ◽  
Acid Base ◽  
Surface Ph ◽  
Middle Cerebral Arteries ◽  
Carbonic Anhydrase Inhibition

The CO2/HCO3– buffer minimizes pH changes in response to acid–base loads, HCO3– provides substrate for Na+,HCO3–-cotransporters and Cl–/HCO3–-exchangers, and H+ and HCO3– modify vasomotor responses during acid–base disturbances. We show here that rat middle cerebral arteries express cytosolic, mitochondrial, extracellular, and secreted carbonic anhydrase isoforms that catalyze equilibration of the CO2/HCO3– buffer. Switching from CO2/HCO3–-free to CO2/HCO3–-containing extracellular solution results in initial intracellular acidification due to hydration of CO2 followed by gradual alkalinization due to cellular HCO3– uptake. Carbonic anhydrase inhibition decelerates the initial acidification and attenuates the associated transient vasoconstriction without affecting intracellular pH or artery tone at steady-state. Na+,HCO3–-cotransport and Na+/H+-exchange activity after NH4+-prepulse-induced intracellular acidification are unaffected by carbonic anhydrase inhibition. Extracellular surface pH transients induced by transmembrane NH3 flux are evident under CO2/HCO3–-free conditions but absent when the buffer capacity and apparent H+ mobility increase in the presence of CO2/HCO3– even after the inhibition of carbonic anhydrases. We conclude that (a) intracellular carbonic anhydrase activity accentuates pH transients and vasoconstriction in response to acute elevations of pCO2, (b) CO2/HCO3– minimizes extracellular surface pH transients without requiring carbonic anhydrase activity, and (c) carbonic anhydrases are not rate limiting for acid–base transport across cell membranes during recovery from intracellular acidification.

Effect of acetazolamide on gas exchange and acid-base control after maximal exercise

1992 ◽  
Vol 72 (1) ◽  
pp. 278-287 ◽  
Author(s):  
J. M. Kowalchuk ◽  
G. J. Heigenhauser ◽  
J. R. Sutton ◽  
N. L. Jones
Keyword(s):  
Carbonic Anhydrase ◽  
Muscle Power ◽  
Inorganic Ions ◽  
Carbonic Anhydrase Activity ◽  
Co2 Production ◽  
Acid Base ◽  
Carbonic Anhydrase Inhibition ◽  
Severe Exercise ◽  
Arterial Plasma ◽  
End Tidal

To investigate the interactions between the systems that contribute to acid-base homeostasis after severe exercise, we studied the effects of carbonic anhydrase inhibition on exchange of strong ions and CO2 in six subjects after 30 s of maximal isokinetic cycling exercise. Each subject exercised on two randomly assigned occasions, a control (CON) condition and 30 min after intravenous injection of 1,000 mg acetazolamide (ACZ) to inhibit blood carbonic anhydrase activity. Leg muscle power output was similar in the two conditions; peak O2 uptake (VO2) after exercise was lower in ACZ (2,119 +/- 274 ml/min) than in CON (2,687 +/- 113, P less than 0.05); peak CO2 production (VCO2) was also lower (2,197 +/- 241 in ACZ vs. 3,237 +/- 87 in CON, P less than 0.05) and was accompanied by an increase in the recovery half-time from 1.7 min in CON to 2.3 min in ACZ. Whereas end-tidal PCO2 was lower in ACZ than in CON, arterial PCO2 (PaCO2) was higher, and a large negative end-tidal-to-arterial difference (less than or equal to 20 Torr) was present in ACZ on recovery. In ACZ, postexercise increases in arterial plasma [Na+] and [K+] were greater but [La-] was lower. Arteriovenous differences across the forearm showed a greater uptake of La- and Cl- in CON than in ACZ. Carbonic anhydrase inhibition with ACZ, in addition to impairing equilibration of the CO2 system to the acid-base challenge of exercise, was accompanied by changes in equilibration of strong inorganic ions. A lowered plasma [La-] was not accompanied by greater uptake of La- by inactive muscle.

Histochemical localization of Na+–K+ ATPase and carbonic anhydrase activity in gills of 17 fish species

1988 ◽  
Vol 66 (11) ◽  
pp. 2398-2405 ◽  
Author(s):  
David M. Conley ◽  
Jon Mallatt
Keyword(s):  
Carbonic Anhydrase ◽  
Atpase Activity ◽  
Carbonic Anhydrase Activity ◽  
Chloride Cells ◽  
Shark Species ◽  
Acid Base ◽  
Pavement Cells ◽  
Leopard Shark ◽  
Biochemical Assays ◽  
Definite Correlation

Activities of two enzymes considered to be involved in NaCl regulation, Na+–K+ ATPase and carbonic anhydrase, were localized in gill epithelia of 14 teleost, 2 agnathan, and 1 shark species through light microscopic histochemistry. Findings were confirmed by use of appropriate inhibitors (ouabain, acetazolamide). Na+–K+ ATPase activity was detected in chloride cells of most marine teleost species (six of eight) and of marine leopard shark and hagfish, but never in freshwater fish gills. In general, this finding agrees with past biochemical assays showing gill Na+–K+ ATPase activity to be highest in marine teleosts. Staining for carbonic anhydrase took one of three patterns among species: gill pavement cells or chloride cells, or both, were stained. Interspecific distribution of these patterns bore little relation to taxonomy or to habitat salinity, although chloride cells of euryhaline teleosts seemed more likely to stain than chloride cells of stenohaline teleosts, freshwater or marine. Given the lack of a definite correlation with salinity, it is concluded that fish gill carbonic anhydrase may not function in NaCl regulation as much as in acid–base regulation; the enzyme's role in preventing systemic pH imbalance is discussed.

Exploring carbonic anhydrase inhibition with multimeric coumarins displayed on a fullerene scaffold

2015 ◽  
Vol 13 (27) ◽  
pp. 7445-7451 ◽  
Author(s):  
Marta Abellán-Flos ◽  
Muhammet Tanç ◽  
Claudiu T. Supuran ◽  
Stéphane P. Vincent
Keyword(s):  
Carbonic Anhydrase ◽  
Carbonic Anhydrases ◽  
Carbonic Anhydrase Inhibition ◽  
Suicide Inhibitors

This study reports the first synthesis of multimeric suicide inhibitors of carbonic anhydrases.

Renal carbonic anhydrase

1982 ◽  
Vol 243 (4) ◽  
pp. F311-F324 ◽  
Author(s):  
D. C. Dobyan ◽  
R. E. Bulger
Keyword(s):  
Carbonic Anhydrase ◽  
Collecting Duct ◽  
Mammalian Species ◽  
Carbonic Anhydrase Activity ◽  
The Body ◽  
Carbonic Anhydrases ◽  
Duct System ◽  
Renal Carbonic Anhydrase ◽  
Membrane Bound ◽  
Editorial Review

Carbonic anhydrase is a zinc metalloenzyme widely distributed throughout the tissues of the body. This enzyme exists in a number of isozymic forms in most mammalian species. Significant advances over the past decade have been made in characterizing the nature of renal carbonic anhydrase. In the kidney, this enzyme is thought to play a pivotal role in urinary acidification and bicarbonate reabsorption. Two distinct isozymes of carbonic anhydrase have now been identified in the mammalian kidney. A soluble cytoplasmic form, similar if not identical to human erythrocyte carbonic anhydrase C, accounts for the bulk of the renal carbonic anhydrase activity. In addition, a membrane-bound form constituting only about 2--5% of the renal activity has been found in the brush border and basolateral fractions of kidney homogenates. The histochemical and immunocytochemical localization of these isozymes along the nephron and collecting duct system of various mammalian species suggests that marked heterogeneity exists. The Editorial Review examines the biochemical and morphological approaches that have been used to elucidate the nature of renal carbonic anhydrase and to assess its distribution along the urinary tubule. Possible physiological roles for the renal carbonic anhydrases are considered for the different segments of the nephron and collecting duct system.

scholarly journals Oxygen isotope exchange between water and carbon dioxide in soils is controlled by pH, nitrate availability and microbial biomass through links to carbonic anhydrase activity

2020 ◽  
Author(s):  
Sam P. Jones ◽  
Aurore Kaisermann ◽  
Jerome Ogee ◽  
Steven Wohl ◽  
Alexander W. Cheesman ◽  
...  
Keyword(s):  
Carbon Dioxide ◽  
Microbial Biomass ◽  
Carbonic Anhydrase ◽  
Oxygen Isotope ◽  
Isotope Exchange ◽  
Microbial Community Composition ◽  
Soil Microbial Communities ◽  
Carbonic Anhydrase Activity ◽  
Carbonic Anhydrases ◽  
Oxygen Isotope Exchange

Abstract. The oxygen isotope composition (δ18O) of atmospheric carbon dioxide (CO2) can be used to estimate gross primary production at the ecosystem-scale and above. Understanding how and why the rate of oxygen isotope exchange between soil water and CO2 (kiso) varies can help to reduce uncertainty in the retrieval of such estimates. The expression and activity of carbonic anhydrases in soils are important drivers of variations in kiso. Here we estimate kiso and measure associated soil properties in laboratory incubation experiments using 44 soils sampled from sites across western Eurasia and northeastern Australia. Observed kiso exceeded theoretical uncatalysed rates indicating the significant influence of carbonic anhydrases on the variability observed among the soils studied. We identify soil pH as the principal source of variation, with greater kiso under alkaline conditions suggesting that shifts in microbial community composition or intra-extra cellular dissolved inorganic carbon gradients induce the expression of more or higher activity forms of carbonic anhydrases. We also show for the first time in soils that the presence of nitrate under acidic conditions reduces kiso, potentially reflecting the direct or indirect inhibition of carbonic anhydrases. This effect was confirmed by a supplementary ammonium nitrate fertilisation experiment conducted on a subset of the soils. Future changes in atmospheric nitrogen deposition or land-use may thus influence carbonic anhydrase activity. Greater microbial biomass also increased kiso under a given set of chemical conditions likely highlighting the ubiquity of carbonic anhydrase expression by soil microbial communities. These data provide the most extensive analysis of spatial variations in soil kiso to date and indicate key controls required to predict variations in kiso at the scales needed to improve efforts to constrain gross primary productivity using the δ18O of atmospheric CO2.

scholarly journals Effect of NaHS on carbonic anhydrase activity of human erythrocyte

2016 ◽  
Vol 7 (3) ◽  
pp. 23-27 ◽  
Author(s):  
Abhijit Bhakta ◽  
Maitreyi Bandyopadhyay ◽  
Sayantan Dasgupta ◽  
Santanu Sen ◽  
Arun Kumar ◽  
...  
Keyword(s):  
Carbonic Anhydrase ◽  
Normal Saline ◽  
Carbonic Anhydrase Activity ◽  
Experimental Models ◽  
Test Tube ◽  
Dependent Manner ◽  
Carbonic Anhydrases ◽  
Medical Sciences ◽  
First Time

Background: In contrast to its role as poison, hydrogen sulfide (H2S) is recently considered as a gaso-transmitter which mediates important physiologic functions in humans. Evidence is accumulating to demonstrate that inhibitors of H2S production or therapeutic H2S donor compounds exert significant effects in various experimental models. Carbonic anhydrases (CA) are a group of zinc-containing metalloenzymes that catalyse the reversible hydration of carbon dioxide. CAs activity in erythrocytes (CAI and CAII) has recently been observed to be associated with various pathological conditions especially in diabetes mellitus, hypertension and lipid disorders. Alteration of this enzyme activity has been reported by the effect of advanced glycation end products methylglyoxal and reduced glutathione.   Aims and Objectives: As H2S, being a mediator of many physiological functions and synthesized in vivo, may affect functions of many intracellular proteins like carbonic anhydrase, the objective of this study is to find out if there is any change in the carbonic anhydrase activity under the effect of H2S- donor NaHS in dose dependant manner using RBC model in vitro.Materials and Methods: Blood sample was collected from forty (40) numbers of healthy volunteers of 18-40 years of in heparin containing vials and packed cells were prepared immediately by centrifugation  The packed erythrocytes were washed three times with normal saline and  diluted (1:10) with the normal saline. One ml each of diluted packed cells was taken in eight test tubes. Serial dilutions of NaHS (1to 250 µMol/L) was added to all the test tubes except for the first test tube where only normal saline was added and   incubated at room temperature for one hour. Haemolysates was prepared from the erythrocytes with equal volume of distilled water in each tube and the CA activity was determined in the haemolysates using standardized method.Results: There is significant increase of CA activity in dose dependent manner under the effect of NaHS and also compared to the activity of hemolysate prepared without NaHS.  Conclusions:Our study for the first time demonstrated that the Carbonic Anhydrase activity of erythrocytes is significantly increases by the effect of NaHS and this study reveals some important biological role of H2S and carbonic anhydrase.Asian Journal of Medical Sciences Vol. 7(3) 2016 23-27

scholarly journals Transgenic expression of carbonic anhydrase III in cardiac muscle demonstrates a mechanism to tolerate acidosis

2019 ◽  
Vol 317 (5) ◽  
pp. C922-C931 ◽  
Author(s):  
Han-Zhong Feng ◽  
J.-P. Jin
Keyword(s):  
Carbonic Anhydrase ◽  
Transgenic Mice ◽  
Intracellular Ph ◽  
Skeletal Muscles ◽  
Ex Vivo ◽  
Physiological Role ◽  
Wild Type Mouse ◽  
Carbonic Anhydrases ◽  
Wild Type ◽  
Carbonic Anhydrase Iii

Carbonic anhydrase III (CAIII) is abundant in liver, adipocytes, and skeletal muscles, but not heart. A cytosolic enzyme that catalyzes conversions between CO2 and [Formula: see text] in the regulation of intracellular pH, its physiological role in myocytes is not fully understood. Mouse skeletal muscles lacking CAIII showed lower intracellular pH during fatigue, suggesting its function in stress tolerance. We created transgenic mice expressing CAIII in cardiomyocytes that lack endogenous CAIII. The transgenic mice showed normal cardiac development and life span under nonstress conditions. Studies of ex vivo working hearts under normal and acidotic conditions demonstrated that the transgenic and wild-type mouse hearts had similar pumping functions under normal pH. At acidotic pH, however, CAIII transgenic mouse hearts showed significantly less decrease in cardiac function than that of wild-type control as shown by higher ventricular pressure development, systolic and diastolic velocities, and stroke volume via elongating the time of diastolic ejection. In addition to the effect of introducing CAIII into cardiomyocytes on maintaining homeostasis to counter acidotic stress, the results demonstrate the role of carbonic anhydrases in maintaining intracellular pH in muscle cells as a potential mechanism to treat heart failure.

Postcapillary changes in blood pH in vivo during carbonic anhydrase inhibition

1977 ◽  
Vol 43 (4) ◽  
pp. 582-590 ◽  
Author(s):  
E. D. Crandall ◽  
A. Bidani ◽  
R. E. Forster
Keyword(s):  
Carbonic Anhydrase ◽  
Carbonic Anhydrase Activity ◽  
Stopped Flow ◽  
Arterial Blood ◽  
Blood Ph ◽  
Pulmonary Capillary ◽  
Carbonic Anhydrase Inhibition ◽  
Glass Ph Electrode ◽  
Electrode Chamber

A rapidly responding stopped-flow glass pH electrode apparatus was used to investigate pH changes in blood in vivo after it exits from an exchange capillary. Arterial blood was drawn from anesthetized animals through the apparatus. Temperature and pH of the blood in the electrode chamber were continuously recorded, both during withdrawal and after flow was stopped. Blood pH did not change after stopping flow in control experiments. When benzolamide (2 mg/kg) was given to inhibit carbonic anhydrase activity available to plasma (e.g., due to lysis) while having less effect on intracellular activity, pH increased 0.02–0.04 (t1/2 approximately 8 s) after stopping flow. Administration of acetazolamide (50 mg/kg) resulted in pH decreasing 0.07–0.10 (t1/2 approximately 15 s) after stopping flow. Ventilation for 1 min with N2 resulted in an increased rise in pH for the benzolamide-treated animals but a decreased fall in pH for the acetazolamide-treated animals. These shifts in arterial blood pH after gas exchange are largely due to disequilibrium of [H+] between red cells and plasma at the end of the pulmonary capillary.

Roles of gill and red cell carbonic anhydrase in elasmobranch HCO3- and CO2 excretion

1987 ◽  
Vol 253 (3) ◽  
pp. R450-R458 ◽  
Author(s):  
E. R. Swenson ◽  
T. H. Maren
Keyword(s):  
Carbonic Anhydrase ◽  
Respiratory Acidosis ◽  
Red Cell ◽  
Acid Base ◽  
Terrestrial Vertebrates ◽  
Carbonic Anhydrase Inhibition ◽  
Normal Metabolism ◽  
Acid Base Status ◽  
Erythrocyte Carbonic Anhydrase ◽  
Co2 Elimination

We studied the roles of gill and erythrocyte carbonic anhydrase in normal CO2 transfer (metabolic CO2 elimination) and in HCO3- excretion during metabolic alkalosis in the resting and swimming dogfish shark, Squalus acanthias. Gill carbonic anhydrase was selectively inhibited (greater than 98.5%) by 1 mg/kg benzolamide, which caused no physiologically significant red cell carbonic anhydrase inhibition (approximately 40%). Enzyme in both tissues was inhibited by 30 mg/kg methazolamide (greater than 99%). Both drugs caused equivalent reductions in HCO3- excretion following an infusion of 9 mmol/kg NaHCO3 as measured by the rate of fall in plasma HCO3- and by transfer into seawater. Methazolamide (red cell and gill carbonic anhydrase inhibition) caused a respiratory acidosis in fish with normal acid-base status, whereas benzolamide (gill carbonic anhydrase inhibition) did not. The only effect observed with benzolamide in these fish was a small elevation in plasma HCO3-. These findings, taken together, suggest that red cell carbonic anhydrase is required for normal metabolic CO2 elimination by the gill. Although carbonic anhydrase is located in the respiratory epithelium, it appears to have no quantitative role in transfer of metabolic CO2 to the environment, a pattern similar to all terrestrial vertebrates. However, carbonic anhydrase in the gill is crucial to this organ's function in acid-base regulation, both in the excretion of H+ or HCO3- generated in normal metabolism and in various acid-base disturbances.

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