Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Renal reabsorption of bicarbonate was studied in Merino ewes during carbonic anhydrase inhibition. Bicarbonate reabsorption was directly proportional to plasma bicarbonate concentration. No tubular maximum for bicarbonate was demonstrated. Elevation of arterial PCO2 or depression of arterial pH caused slight increases in bicarbonate reabsorption. The data suggest that bicarbonate is reabsorbed by 2 distinct processes. The quantitatively more significant process may involve ionic reabsorption of bicarbonate secondary to Na+ reabsorption and a relatively minor part of bicarbonate reabsorption may be secondary to H+ secretion.
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PMID:The effect of carbonic anhydrase inhibition on bicarbonate reabsorption. 0 67

The effects of anion-transport inhibitors on volume reabsorption, and total CO(2) concentrations were examined by in vivo microperfusion of superficial proximal convoluted tubules of rats. The luminal perfusion solution was a high-chloride, low-bicarbonate solution like that in the in vivo late proximal tubule. The anion-transport inhibitors were only added to the luminal perfusion solutions. In tubules perfused with the control high-chloride solution, the rate of volume reabsorption (J(v)) was 2.3+/-0.2 nl/mm.min (n = 18), and the collected total CO(2) concentration was 4.0+/-0.3 mM. Furosemide (3 mM) caused a marked reduction in volume reabsorption to 0.8+/-0.3 nl/mm.min (n = 20) and only a slight increase in the total CO(2) concentration of collected samples of perfusate (7.8+/-0.5 mM). 0.8 mM acetazolamide caused a more pronounced rise in the collected total CO(2) concentrations to 10.7+/-0.5 mM but only a slight fall in J(v) to 1.7+/-0.3 nl/mm.min (n = 19). Hence, we inferred that inhibition of carbonic anhydrase only partially accounted for the inhibition of J(v) by furosemide. 4-acetamido-4'-iso-thiocyanato-stilbene-2,2'-disulphonic acid (0.1 mM), a well-characterized inhibitor of erythrocyte anion exchange mechanisms, also reduced J(v) to 1.6+/-0.3 nl/mm.min (n = 15) without changing the total CO(2) concentrations of the collected perfusates (3.6+/-0.4 mM). The effect of 4-acetamido-4'-iso-thiocyanato-stilbene-2,2'-disulphonic acid on volume reabsorption could not be explained by carbonic anhydrase inhibition because there was no increase in the total CO(2) concentration of the collected fluids. Furosemide did not significantly inhibit the rate of tracer glucose efflux out of the tubules, which suggests that the effect of furosemide on volume reabsorption was not a result of some nonspecific depression of active sodium transport. These results are discussed with respect to the possible effects of anion-transport inhibitors on the paracellular shunt pathway, active sodium reabsorption, and neutral sodium chloride transport.
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PMID:Effects of anion-transport inhibitors on NaCl reabsorption in the rat superficial proximal convoluted tubule. 45 69

1. Bicarbonate transport across human red cell membranes was studied between 0 and 10 degrees C at alkaline pH values by determining the efflux of 14C-labelled bicarbonate from resealed erythrocyte ghosts. Transfer of labelled CO2 was eliminated as a source of error, when formation of intracellular 14CO2 was inhibited with carbonic anhydrase inhibitors. The study showed that there are no fundamental differences between the characteristics of bicarbonate and of chloride self-exchange as has been inferred from previous studies of chloride-bicarbonate exchange. 2. Efflux of radioactivity could be reduced more than 99% by reversible and irreversible inhibitors of anion transport. Inhibition of both chloride and bicarbonate self-exchange was linearly related to the binding of 4,4'-diisothiocyanostilbene-2,2'-disulphonic acid (DIDS) to the membranes. Complete (i.e. greater than 99%) inhibition was obtained after binding of 1.2 x 10(6) DIDS molecules per cell. 3. Bicarbonate self-exchange proved a saturable function of bicarbonate concentration, with a maximum at external and internal concentrations of approximately 100 mM, showing self-depression at higher bicarbonate concentrations, and half-maximum exchange flux at a concentration of 10 mM. The results were consistent with the hypothesis that the exchange mechanism has two anion binding sites, one mediating ion transport and the other causing transport inhibition. 4. Maximum exchange flux of bicarbonate was about 30% larger thant that of chloride, and the affinity of bicarbonate for the transport site was about three times larger than that of chloride. The apparent activation energy of bicarbonate exchange was 28 kcal/mole, the same order of magnitude as found for other inorganic anions between 0 and 10 degrees C. 5. The ability of other inorganic anions to exchange with bicarbonate decreased in the sequence Cl greater than NO3 greater than F greater than Br greater than or equal to I, corresponding to the sequence of the rate of self-exchange of halides. 6. Counter-transport of bicarbonate could be driven by a chloride gradient, when ghosts containing KCl were suspended in a medium containing traces of labelled bicarbonate in addition to a non-permeating anion. Concentration ratios (ci/co) up to about 1000 could be obtained. 7. It is concluded that bicarbonate is transported by the inorganic anion exchange mechanism of the erythrocyte membrane. The slight differences between the exchange kinetics of chloride and bicarbonate were explained by differing affinities of the two anions for the two anion binding sites of the transport system.
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PMID:Bicarbonate exchange through the human red cell membrane determined with [14C] bicarbonate. 51 56

Thirty-nine cases of decreased libido in glaucoma patients on carbonic anhydrase inhibitors are reported. This symptom completely reversed or markedly improved after discontinuation of the drug in all cases. Twelve of these patients restarted their carbonic anhydrase inhibitor medication which resulted in a recurrence of decreased libido symptoms. There were 3 cases of impotency which reversed after discontinuation of the drug. Most likely, these symptoms are a result of the malaise and depression occurring in some patients on carbonic anhydrase inhibitor therapy.
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PMID:Decreased libido--a side effect of carbonic anhydrase inhibitor. 55 49

Hansen's membrane manometer method for measuring plasma colloid osmotic pressure was used to obtain the osmolality changes of dogs breathing different levels of CO2. Osmotic pressure was converted to osmolality by calibration of the manometer with saline and plasma, using freezing point depression osmometry. The addition of 10 vol% of CO2 to tonometered blood caused about a 2.0 mosmol/kg H2O increase of osmolality, or 1.2% increase of red blood cell volume. The swelling of the red blood cells was probably due to osmosis caused by Cl- exchanged for the HCO3- which was produced rapidly by carbonic anhydrase present in the red blood cells. The change in colloid osmotic pressure accompanying a change in co2 tension was measured on blood obtained from dogs breathing different CO2 mixtures. It was approximately 0.14 mosmol/kg H2O per Torr Pco2. The corresponding change in red cell volume could not be calculated from this because water can exchange between the plasma and tissues.
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PMID:Colloid osmotic pressure changes of dog's blood exposed to different mixtures of CO2 and air. 63 65

Japanese quail (Coturnix japonica) were fed different levels of pesticide in their diets for 15 weeks. The levels of pesticide used were 25, 50, 100, 200 p.p.m. DDE 25, 50, 100, 200 p.p.m. DDT and 50 p.p.m. PCB. Carbonic anhydrase activities were analyzed in the shell glands and blood; pesticide concentration in the eggs of the first experiment was measured; egg weight, shell weight and shell thickness were also measured. No depression in growth was observed at any levels of pesticides used. Quail fed 200 p.p.m. DDE showed a high mortality rate after 10--12 weeks on the diet, while other levels produced no increase in death rate. Lower levels of DDT and DDE (25 and 50 p.p.m.) had no significant effect on egg shell weight or thickness. Higher levels (100 and 200 p.p.m) of DDT and DDE produced a small increase in shell weight and a 5 per cent decrease in shell thickness and were associated with increased shell breakage. At levels of 25 p.p.m. and 50 p.p.m. DDE, the activity of carbonic anhydrase in the shell gland was significantly increased. At levels of 200 p.p.m. DDE and 100 p.p.m. DDT in the diet, the activity of carbonic anhydrase was decreased by 12--15 per cent. A 50 per cent reduction in carbonic anhydrase activity in the shell gland seemed to be necessary for an increased production of soft shelled eggs when it was induces by sulfanilamide. Pesticide residues in the eggs of Japanes quail up to about 300 p.p.m. DDE and 150 p.p.m. DDT were not associated with any change in egg shell thickness. At about 600 p.p.m. DDE and 500 p.p.m. DDT in the eggs, corresponding to 100 and 200 p.p.m. in the diet, the egg shell thickness was reduced by 5 per cent. PCB at 50 p.p.m. produced a small decrease (4.5 per cent) in shell thickness and an increase in the percentage of cracked eggs.
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PMID:Effect of chlorinated hydrocarbons on shell gland carbonic anhydrase and egg shell thickness in Japanese quail. 80 67

Multiple serum chemical values were examined in 92 patients with chronic glaucoma who were treated with the carbonic anhydrase inhibitors (CAIs) acetazolamide or methazolamide, seeking relationships between serum composition and symptomatic side effects. Of the 92 patients, 44 complained of a symptom-complex of malaise, fatigue, weight loss, depression, anorexia, and loss of libido, which we have found most commonly to threaten continuation of therapy. Patients who had this symptom complex were significantly more acidotic than those without it. Ten of 24 patients who had chemical evidence of excessive acidosis reported a dramatic alleviation of symptoms when sodium bicarbonate was administered, although their serum CO2-combining power changed little. There was no correlation of the symptom complex with serum potassium concentration, except in a few patients who were simultaneously receiving chlorothiazide diuretics for systemic hypertension and who became frankly hypokalemic.
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PMID:Carbonic anhydrase inhibitor side effects. Serum chemical analysis. 88 13

1. Inhibition of carbonic anhydrase by acetazolamide in alpha-chloralose-anaesthetized cats, in a region of the brain stem co-extensive with the glycine-sensitive area, intermediate chemosensitive area, and probably C1 catecholaminergic neurones produces hypotension, bradycardia and depression of the central respiratory drive. 2. These responses are concentration dependent, and can still be observed when the enzyme substrate (CO2) is elevated. Therefore, in both the hypercapnic and the normocapnic condition, similar responses in arterial blood pressure, heart rate and respiratory rate are observed when acetazolamide is topically applied to the glycine-sensitive area. 3. To investigate further the contribution of peripheral baro-, chemo- and cardiopulmonary receptors to these responses, acetazolamide was topically applied to the glycine-sensitive area under three different conditions: intact gallamine-paralysed (5 mg kg-1 h-1) and artificially ventilated (A), sinoaortic denervated (B), and sinoaortic denervated plus bilaterally vagotomized cats (C). Under all conditions, similar responses were observed. The fall in arterial blood pressure was 75 +/- 11 (A), 90 +/- 13 (B), and 75 +/- 9 mmHg (C). Changes in heart rate during acetazolamide application were -23 +/- 6, -20 +/- 8, and -26 +/- 6 beats min-1, respectively. The decreases in respiratory rate were 9 +/- 2 (A), 11 +/- 2 (B), and 11 +/- 2 breaths min-1 (C). 4. The data indicate that the responses to topical application of acetazolamide are mainly due to its central action at the glycine-sensitive area and are not influenced by peripheral baroreceptor and chemoreceptor inputs.
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PMID:Cardiorespiratory effects induced by acetazolamide on the ventromedullary surface of the cat. 211 93

Double-barrel ion-sensitive microelectrodes were used to measure activity-related changes in extracellular pH (pHe), potassium and calcium concentration ([K+]e and [Ca2+]e) in the spinal dorsal horns of frogs. Repetitive stimulation (30-100 Hz) of the dorsal root evoked transient acidification in the lower dorsal horn by 0.25 pH units, which was accompanied by an increase in [K+]e by 4-5 mmol/l and a decrease in [Ca2+]e by 0.5 mmol/l. The pHe changes were found to have a typical depth profile and increased with the stimulation frequency, intensity and duration. The maximum of pHe changes was reached in 25-30 s of stimulation, and when stimulation continued further no greater pHe changes were achieved. Similarly as the K+ and Ca2+ transients, the pHe reached a ceiling level, which was 0.2-0.25 pH units more acid than the pH of the Ringer solution. The poststimulation K+ undershoot below the resting K+ level (3 mmol/l) was accompanied by an alkaline shift before the original pH base line. The rise time of the pHe changes was slower than that of [K+]e and [Ca2+]e changes. However, the redistribution of all the ionic changes had a similar time course. The clearance of changes in [K+]e and pHe was slowed by ouabain. The depression of the acid shift required higher concentrations of ouabain than the depression of the alkaline shifts. Acetazolamide, a carbonic anhydrase inhibitor, depressed the acid and enhanced the alkaline shift. Superfusion of the cord with elevated [K+]e was accompanied by a prompt and progressive acid shift, the lowering of [K+]e by an alkaline shift. The stimulus-evoked K+ increase and acid shift were depressed during the elevated [K+]e, while the alkaline shift was enhanced. Spontaneous elevations of [K+]e were accompanied by acid shifts of a similar time course. The results are discussed in terms of stimulus-evoked changes in extracellular strong ion differences [SID]e, and of their possible physiological significance.
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PMID:Stimulation-evoked changes in extracellular pH, calcium and potassium activity in the frog spinal cord. 297 88

There is as yet no convincing evidence that acetazolamide, a carbonic anhydrase inhibitor, is effective in obstructive sleep apnoea. A study was therefore designed to examine the effect of acetazolamide (250 mg/day) on sleep events and ventilatory control during wakefulness in nine patients with the sleep apnoea syndrome. In eight of the nine patients the apnoea index and the total duration of apnoea were reduced by acetazolamide, and the mean (SEM) apnoea index of all patients changed from 25.0 (6.7) to 18.1 (5.8) episodes an hour. Furthermore, the total time of arterial oxygen desaturation (SaO2)--more than 4% depression in SaO2 from the baseline sleeping level--divided by total sleep time was also significantly decreased and its mean (SEM) value improved from 24.1 (7.9) to 13.6 (4.8)% of total sleep time. Five of the seven patients with varying degrees of daytime hypersomnolence had their symptoms obviously improved. There was no patient whose predominant type of apnoea was converted from the obstructive to the central type, or vice versa. In the studies of wakefulness, metabolic acidosis, an increase of arterial oxygen tension (PaO2) and a decrease of arterial carbon dioxide tension (PaCO2) were observed. The slopes of the occlusion pressure response and the ventilatory response to carbon dioxide increased, and the carbon dioxide ventilatory response line shifted to the left. It is suggested that acetazolamide cannot remove apnoea completely but has a beneficial effect in mild cases of obstructive sleep apnoea through an augmentation of central (CO2, H+) drive and a stabilising effect on ventilatory control.
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PMID:Effects of acetazolamide in patients with the sleep apnoea syndrome. 312 12


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