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

Human spermatozoa contain choline acetyltransferase (ChA), acetylcholinesterase and acetylcholine (ACh). There is no storage pool for ACh in spermatozoa. Therefore, ChA inhibitors should exhibit dramatic effects in the alteration of levels and turnover of ACh and sperm motility. The effects of two groups of ChA inhibitors, 2-benzoylethyltrimethylammonium (BETA) and related compounds and halogenoacetylcholines (cholinesters of iodo-, bromo- and chloroacetic acids; XACh, where X = l, Br or Cl), on the motility index of human ejaculated sperm were studied. These investigations gave the following results: 1) BETA was a potent inhibitor of ChA from monkey brain (I50, 4.8 x 10(-6) M), homogenates of rat spermatozoa (I50, 6.5 x 10(-5) M) and homogenates of human spermatozoa (I50, 5.6 x 10(-5) M). It decreased the motility index of human spermatozoa (I50, 8.5 x 10(-8) M) at concentrations higher than 10(-8) M after a contact time of 5 to 60 min. It decreased the motility index of human spermatozoa by about 80% after 5 min and by 95% after 1 hr at a concentration of 10(-6) M. 2) There was a positive relationship between the inhibition of ChA and the depression of the motility index of human spermatozoa among these inhibitors. Both the number of motile cells and the graded motility were decreased. 3) All ChA inhibitors studied are quaternary ammonium compounds that do not significantly cross membrane barriers. 4) Both human sperm cells and human sperm cell homogenates had the same ChA activity. 5) Seventy-five percent of ChA activity could be washed away from human spermatozoa. 6) The same amount of ChA inhibition was observed when BETA was added to the homogenate of sperm cells or whole sperm cells. All of these observations indicate that sperm cell ChA is accessible to BETA and related quaternary ammonium compounds. These studies indicate that ACh is possibly synthesized by the tail and is a local hormone in the coordination of contraction and relaxation cycles of spermatozoan flagella.
 ...
PMID:Inhibition of human sperm motility by inhibitors of choline acetyltransferase. 746 54

Pyrimidine nucleoside catabolism in the human pathogen Sphingomonas paucimobilis was studied. It was observed that S. paucimobilis was only capable of utilizing cytidine or deoxycytidine as a sole nitrogen source when glucose served as the carbon source. Thinlayer chromatographic analyses of cytidine and uridine catabolic products revealed that the enzymes cytidine deaminase and uridine phosphorylase were active in the extracts prepared from S. paucimobilis cells. The levels of cytidine deaminase and cytosine deaminase activities were lowered after growth on cytidine or deoxycytidine as a nitrogen source instead of ammonium sulfate. Uridine phosphorylase activity increased more than 4-fold after growth on deoxycytidine as a nitrogen source while growth on the nitrogen source cytidine caused a depression in phosphorylase activity.
 ...
PMID:Pyrimidine nucleoside catabolism in Sphingomonas paucimobilis: role of cytidine deaminase and uridine phosphorylase. 760 8

Chronic hyperammonemia is known to lead to pathological forms of astrocytes. To test the influence of these changes on the neurotoxicity of ammonia, the glial metabolic poison fluoroacetate (FA) was applied locally, through microdialysis to the hippocampal dentate gyrus. The penetration of ammonia into the brain following the i.p. injection of 7.8 mmol/kg NH4 acetate was evaluated by measuring the ammonia and glutamine content of the microdialysate. Field EPSPs (fEPSPs) evoked by perforant path stimulation were recorded 1.5 mm from the microdialysis probe. When 20 mM FA was perfused, NH4 acetate injection increased the ammonia efflux by 300% and decreased fEPSPs by 40%, but glutamine concentration remained low. With no FA in the microdialysate, NH4 acetate treatment increased the efflux of ammonia by only 60%, did not affect fEPSPs but doubled glutamine efflux. Arterial ammonia content, as measured by microdialysis in the common carotid, increased 4-5 fold following i.p. administration of NH4 acetate, while arterial glutamine was not elevated. Systemically administered FA did not affect either of these changes significantly, but slightly reduced arterial pH. These observations indicate that FA applied by microdialysis acted locally on astrocytes and therefore impaired astrocytic function contributes to the development of hepatic encephalopathy by facilitating the entry of ammonia into the brain. Inhibition of excitatory synaptic transmission by elevated brain ammonia may underlay CNS depression in hepatic encephalopathy.
 ...
PMID:Astrocytes and the entry of circulating ammonia into the brain: effect of fluoroacetate. 819 41

A technique for the determination of the threshold concentrations of chemical substances for elicitation of spreading depression is described. The technique minimizes the interference of mechanical stimulating effects and alterations in the susceptibility of the retina to spreading depression due to changes in unstirred layers at the liquid-tissue interphase. The following threshold concentrations were shown to elicit the wave: 8000-10000 microM KCl, 100-200 microM sodium glutamate, 5-10 microM sodium kainate, 10-20 microM sodium N-methyl-aspartate, 600-1200 microM (NH4)2SO4 and 400-600 microM BaCl2. Variations of K+ or Mg2+ concentration in the standard Ringer solution that may cause an increase or decrease of spreading depression velocity have an inverse effect on the threshold for elicitation of the reaction.
 ...
PMID:Threshold determination of spreading depression evoking substances in the retina in vitro. 829 24

The action of the angiotensin-converting enzyme (ACE) inhibitor lisinopril on the consequences of myocardial reoxygenation and oxidative damage was assessed in cultured chick embryonic ventricular cardiomyocytes. Lisinopril, 10(-8) M to 10(-6) M, produced a significant (P < 0.05) dose-dependent enhancement of the restoration of contractile frequency occurring during myocardial reoxygenation but did not alter the depression in contractile frequency during hypoxia. Lisinopril significantly (P < 0.05) shifted the dose-response relationship of ammonium persulfate-induced reduction in cardiac contractile frequency. Lisinopril significantly (P < 0.05) reduced the effect of another oxidative agent, tertbutylhydroperoxide which produced a time-dependent reduction in cardiac contractile frequency. Lisinopril did not alter cardiac contractile frequency in the absence of hypoxia or ammonium persulfate or tertbutylhydroperoxide. The viability of cardiomyocytes, assessed by trypan blue exclusion, paralleled the changes in cardiac contractile frequency. Lisinopril significantly (P < 0.05) improved viability of cardiomyocytes exposed to either ammonium persulfate or tertbutylhydroperoxide. Lisinopril did not display any antioxidant properties against the free radical alpha,alpha-diphenyl-beta-picrylhydrazyl. These data suggest that lisinopril accelerates the recovery of cardiomyocytes during reoxygenation and blunts the effects of oxidative agents through mechanisms involving the endogenous renin angiotensin system and/or a direct cellular action.
 ...
PMID:Lisinopril increases the recovery during reoxygenation and resistance to oxidative damage in cardiomyocytes. 840 86

Rat hippocampal slices were exposed for 30 min to each of three levels of increased osmolarity (pi o), achieved by adding 25, 50 or 100 mM mannitol to the bathing solution. The interstitial volume (ISV) determined as the relative volume of dilution of the probe ion, tetra-methyl-ammonium (TMA+), increased markedly, indicating cell shrinkage. Tissue resistance (Ro) decreased only slightly with increasing pi o. The discrepancy between ISV increase and Ro decrease suggests increased electrical resistance of cell membranes. TMA+ dilution appears to be a more reliable measure of ISV than is Ro. During recovery from hypertonic treatment the previously expanded ISV frequently shrank, suggesting post-hypertonic cell swelling. Hypertonic treatment significantly depressed orthodromically transmitted population spikes and extracellular synaptic potentials (fEPSPs), and the degree of depression varied with the increase in pi o. Changing recording condition due to reduced Ro could not account for the depression of population spikes and fEPSPs. Following return to normal pi o, orthodromic population spikes frequently overshot initial control amplitude. An isolated episode of spreading depression occurred in about half of the slices following exposure to the most severely hypertonic solution. At the end of 2.5 h recovery, orthodromic spikes did not significantly differ from those of untreated control slices observed for the same length of time. We conclude that synaptic transmission is depressed by elevation of pi o, and the depression is concentration dependent and reversible.
 ...
PMID:The effect of graded hypertonia on interstitial volume, tissue resistance and synaptic transmission in rat hippocampal tissue slices. 884 75

Manipulations of pH and electrical gradients in a perfused preparation were used to analyze the factors controlling ammonia distribution and flux in trout white muscle after exercise. Trout were exercised to exhaustion, and then an isolated-perfused white muscle preparation with discrete arterial inflow and venous outflow was made from the posterior portion of the tail. The tail-trunks were perfused with low (7.4)-, medium (7.9)-, and high (8.4)-pH saline, achieved by varying HCO3- concentration ([HCO3-]) at constant Pco2. Intracellular and extracellular pH, ammonia, CO2, K+, Na+, and Cl- were measured. Muscle intracellular pH was not affected by changes in extracellular pH. Increasing extracellular pH caused a decrease in the transmembrane NH3 partial pressure (PNH3) gradient and a decrease in ammonia efflux. When extracellular K+ concentration was increased from 3.5 to 15 mM in the medium-pH group, a depolarization of the muscle cell membrane potential from -92 to -60 mV and a 0.1-unit depression in intracellular pH occurred. Ammonia efflux increased despite a marked reduction in the PNH3 gradient. Amiloride (10(-4) M) had no effect, indicating that Na+/H(+)-NH4+ exchange does not participate in ammonia transport in this system. A comparison of observed intracellular-to-extracellular ammonia distribution ratios with those modeled according to either pH or Nernst potential distributions supports a model in which ammonia distribution across white muscle cell membranes is affected by both pH and electrical gradients, indicating that the membranes are permeable to both NH3 and NH4+. Membrane potential, acting to retain high levels of NH4+ in the intracellular compartment, appears to have the dominant influence during the postexercise period. However, at rest, the pH gradient may be more important, resulting in much lower intracellular ammonia levels and distribution ratios. We speculate that the muscle cell membrane NH3-to-NH4+ permeability ratio in trout may change between the rest and postexercise condition.
 ...
PMID:Ammonia movement and distribution after exercise across white muscle cell membranes in rainbow trout. 885 99

Changes in the rates of oxygen consumption and ammonium excretion, in intra- and extracellular acid-base status and in the rate of H+-equivalent ion transfer between animals and ambient water were measured during environmental hypercapnia in the peanut worm Sipunculus nudus. During exposure to 1 % CO2 in air, intracellular and coelomic plasma PCO2 values rose to levels above those expected from the increase in ambient CO2 tension. Simultaneously, coelomic plasma PO2 was reduced below control values. The rise in PCO2 also induced a fall in intra- and extracellular pH, but intracellular pH was rapidly and completely restored. This was achieved during the early period of hypercapnia at the expense of a non-respiratory increase in the extracellular acidosis. The pH of the extracellular space was only partially compensated (by 37 %) during long-term hypercapnia. The net release of basic equivalents under control conditions turned to a net release of protons to the ambient water before a net, albeit reduced, rate of base release was re-established after a new steady state had been achieved with respect to acid-base parameters. Hypercapnia also affected the mode and rate of metabolism. It caused the rate of oxygen consumption to fall, whereas the rate of ammonium excretion remained constant or even increased, reflecting a reduction of the O/N ratio in both cases. The transient intracellular acidosis preceded a depletion of the phosphagen phospho-l-arginine, an accumulation of free ADP and a decrease in the level of Gibbs free energy change of ATP hydrolysis, before replenishment of phosphagen and restoration of pHi and energy status occurred in parallel. In conclusion, long-term hypercapnia in vivo causes metabolic depression, a parallel shift in acid-base status and increased gas partial pressure gradients, which are related to a reduction in ventilatory activity. The steady-state rise in H+-equivalent ion transfer to the environment reflects an increased rate of production of protons by metabolism. This observation and the reduction of the O/N ratio suggest that a shift to protein/amino acid catabolism has taken place. Metabolic depression prevails, with completely compensated intracellular acidosis during long-term hypercapnia eliminating intracellular pH as a significant factor in the regulation of metabolic rate in vivo. Fluctuating levels of the phosphagen, of free ADP and in the ATP free energy change values independent of pH are interpreted as being correlated with oscillating ATP turnover rates during early hypercapnia and as reflecting a tight coupling of ATP turnover and energy status via the level of free ADP.
 ...
PMID:Acid-base regulation, metabolism and energetics in sipunculus nudus as a function of ambient carbon dioxide level 939 Sep 35

Phagocytosis of IgG-coated erythrocytes (EIgG) can depress several macrophage functions. Our previous studies have suggested that this macrophage dysfunction may be due to an oxidative stress caused by the interaction of hemoglobin-derived iron with superoxide and/or hydrogen peroxide. Since lysosomotropic agents are capable of altering iron handling by macrophages, the present study evaluated the ability of these agents to prevent the macrophage dysfunction and lipid peroxidation caused by a phagocytic challenge with EIgG. Elicited rat peritoneal macrophages showed a depression of PMA-stimulated hydrogen peroxide production, calcium ionophore-stimulated arachidonate release and Fc receptor-mediated phagocytosis. The lysosomotropic agents; chloroquine, quinacrine, ammonium chloride and methylamine all prevented the depression of hydrogen peroxide production and arachidonate release but did not alter the depression of phagocytic function. These agents also prevented the increase in lipid peroxidation products caused by a phagocytic challenge with EIgG. These results suggest that the ability of lysosomotropic agents to prevent some aspects of macrophage dysfunction after a phagocytic challenge may be due to their ability to block the oxidative stress caused by the challenge.
 ...
PMID:Lysosomotropic agents ameliorate macrophage dysfunction following the phagocytosis of IgG-coated erythrocytes: a role for lipid peroxidation. 942 9

A phagocytic challenge with immunoglobulin G (IgG)-coated erythrocytes (EIgGs) has been shown to cause a subsequent depression of macrophage respiratory burst capacity and phagocytic function. The present study evaluated the hypothesis that this macrophage dysfunction is caused by an oxidative stress. An oxidative stress induced by ferric ammonium citrate (FAC) plus cumene hydroperoxide (CHP) caused a depression of macrophage function that was attenuated by antioxidants and iron chelators. In contrast, the same antioxidants and iron chelators did not alter changes caused by a challenge with EIgGs. EIgG challenge caused an increase in lipid peroxidation but failed to deplete glutathione (GSH) or decrease the activity of glyceraldehyde-3-phosphate dehydrogenase (GA-3-PD), suggesting that there was only a slight oxidative stress. Inhibition of the Fc gamma receptor (Fc gammaR) stimulated respiratory burst by removing calcium during the challenge did not attenuate the changes caused by an EIgG challenge. A phagocytic challenge with nonerythrocyte particles, IgG-coated beads (BIgGs), did not depress the respiratory burst capacity but did depress phagocytic function. Fc gammaR expression was depressed following a phagocytic challenge but not an oxidative stress. Thus, an oxidative stress can depress macrophage function, but the dysfunction caused by a phagocytic challenge with EIgGs involves Fc gammaR depletion and the erythrocyte contents rather than an oxidative stress.
 ...
PMID:Role of an oxidative stress in the macrophage dysfunction caused by erythrophagocytosis. 1064 41


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>