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)

These experiments were designed to examine the mechanisms involved in the renal excretion of the non-nutritive sweetener, saccharin. Renal transport of saccharin in female rats was quantitatively evaluated using renal cortical slices in vitro and renal clearances in vivo. Renal cortical slices actively accumulated saccharin. Accumulation was oxygen dependent, saturable and reduced in the presence of metabolic inhibitors (2,4-dinitrophenol and sodium azide) and other organic anions 1p-aminohippurate (PAH) and probenecid]. Furthermore, addition of acetate or lactate to the medium stimulated saccharin uptake whereas reducing potassium concentration in the medium significantly decreased saccharin accumulation. Addition of saccharin to medium containing PAH and N-methylnicotinamide produced a dose-related depression of PAH accumulation. Although N-methylnicotinamide accumulation also was reduced, the depression was not dose-related. The saccharin/inulin clearance ratio of 3.76 indicates that saccharin, like PAH, undergoes tubular secretion. These findings suggest that the primary route of renal elimination of saccharin is active tubular secretion. It is also suggested that saccharin and PAH may share a common transport system.
 ...
PMID:Renal tubular transport of saccharin. 14 38

The understanding of the effects of cannabinoids in human subjects has been obscured by a lack of knowledge about how the various active principles from marijuana act at the cellular level in the brain. For this reason the present study was undertaken to determine the effects of cannabinoids on the enzymes associated with the synaptic membranes. Electron micrographic analysis was performed to determine the purity of synaptic membrane preparations from rat brain, and subsequently such preparations were subjected to additions of ethanol, Tween-80, 80% glycerol, and either delta-tetrahydrocannabinol, 11-hydroxy-delta-tetrahydrocannabinol, or cannabinol. Both sodium and potassium activated ATPase (Na, K-ATPase), and Mg-ATPase were measured as the micrometer orthophosphate (P) released per minute per microgram membrane protein and these specific activities of the enzymes expressed as absolute values and as the percentage depression brought about by the cannabinoids. The ATPase spcific activities are taken from the rate curve over a 30-min incubation time. Additionally, synaptic membrane acetylcholineesterase specific activity was measured by continuous rate enzyme assay. While as low as 10 M delta-tetrahydrocannabinol showed appreciable decrements in both the membrane-bound ATPases, the other cannabinoids did not show such a great depression in enzyme activity. The specific activity of acetylcholinesterase, which is weakly bound to the membrane, showed only slight or no changes in activity with the various cannabinoids. It was additionally shown that the cannabinoids, delta-tetrahydrocannabinol in particular, bound to the synaptic membranes almost irreversibly in the in vitro system, and that the vehicle for dissolving the cannabinoids, while used as background control values when calculating the percentage decrements in enzyme specific activity, did vary the effects on the ATPase enzymes in particular. These data are discussed in relation to psychotomimetic activity of the cannabinoids.
 ...
PMID:Effects of cannabinoids on synaptic membrane enzymes. I. In vitro studies on synaptic membranes isolated from rat brain. 14 40

Platelets were examined to enable a simultaneous investigation to be made of indolylamine and electrolyte metabolism in affective disorder. No significant differences were detected in either platelet membrane ATPase or adenyl cyclase specific activity in any of the groups of patients studied, when compared with appropriate controls. A reduced Vmax and y for the 5-hydroxy-tryptamine uptake process into platelets was observed in both unipolar and bipolar depressed groups. The Km for this process was not significantly different in any of the patients from that found in control subjects. Lithium therapy was shown not to influence significantly any of the platelet parameters examined. It is suggested that membrane enzyme changes found in some peripheral cells in patients suffering from affective disorder, i.e. reduced Na+ + K+ - ATPase activity in erythrocytes in depression, is not common to all peripheral cells and may or may not reflect central nervous system changes.
 ...
PMID:Studies on human blood platelets in affective disorder. 15 82

Eight 2-arylimino-3-(3-N-morpholinopropyl) thiazolid-4-ones were synthesized from the corresponding 1-aryl-3-(3-N-morpholinopropyl) thiocarbamides, characterized, and tested for their effects on the cellular respiratory activity of rat brain homogenates. All substituted 4-thiazolidones selectively inhibited nicotinamide adenine dinucleotide (NAD)-dependent oxidations of pyruvate, citrate, DL-isocitrate, alpha-ketoglutarate, malate, beta-hydroxybutyrate, L-glutamate, and NADH, while the NAD-independent oxidation of succinate remained unaltered. All thiazolidones possessed some degree of anticonvulsant activity against pentylenetetrazol-induced convulsions, and the protection afforded by these compounds at a dose of 100 mg/kg ranged from 30 to 80%. The low toxicity possessed by most of these thiazolidones was reflected by their approximate LD-50 values from 300 mg/kg to greater than 1000 mg/kg. In the present study, the anticonvulsant activity possessed by these substituted 4-thiazolidones was unrelated to their ability to inhibit selectively the NAD-dependent oxidations by rat brain homogenates. These thiazolidones exhibited depression of the CNS activity which, in some cases, was associated with the increase in respiration. All thiazolidones potentiated pentobarbital (sodium) sleeping time in mice when administered in a dose of 100 mg/kg.
 ...
PMID:Substituted thiazolidones: selective inhibition of nicotinamide adenine dinucleotide-dependent oxidations and evaluation of their CNS activity. 16 47

The functional zonation in the adrenocortical tissue of the duck was experimentally investigated after chronic administration of corticosteroids of different types (corticosterone, desoxycorticosterone, dexamethasone) and salt loading (chlorides of sodium and potassium). The cytomorphology of the interrenal cells belonging to subcapsular and central zones was explored by light- and electron microscopy and by biochemical analysis of plasma corticosterone. Corticoid-induced involution of the interrenal tissue, or hyperactivity elicited by salt loading were evident in both subcapsular and central regions of the gland. In the duck the adrenocortical tissue appears to be devoid of steroidogenic functional differentiation. The modifications of different cellular organelles and inclusions can be explained in the light of known concepts about corticosteroid metabolism. The depression of plasma corticosterone titre in corticosteroid-treated animals agrees with the image of cytological inhibition. The lowered corticosterone value in KCl-loaded ducks signifies increased peripheral metabolism of this hormone. The hypercorticosteronemia in NaCl-loaded ducks is probably related to activation of the nasal gland under osmotic stress.
 ...
PMID:Adrenocortical response in the duck exposed to corticosteroid administration and salt loading. 16 78

Lithium (Li+) chloride, 2 to 3 mEq. per kilogram of body weight, was administered intraperitoneally to normal Wistar rats daily for 4 to 66 days. This resulted in a marked reduction in urine osmolality (Uosm.) and increase in the excretion of water, Na+, K+, uric acid, and phosphate. The excretion of uric acid and potassium was a direct function of UNaV. The magnitude of depression in urine osmolality was significantly related to the rate of excretion of lithium in the urine, suggesting that the change in water reabsorption is dependent on the presence of the ion in the luminal side of the tubule. During 2 per cent saline diuresis, Li+-treated rats achieved less fractional free water reabsorption (TcH2O/GFR times 100) at any level of fractional osmolar clearance (Cosm./GFR times 100) than normal rats. On the other hand, during 0.225 per cent saline diuresis, fractional free water clearance (CH2O/GFR times 100) was normal over a wide range of fractional urine flow (V/GFR times 100), indicating intact function of the ascending limb of the loop of Henle. The intravenous infusion of vasopressin (VP) or dibutyryl cyclic-adenosine monophosphate (dcAMP) to Li+-treated rats resulted in a modest rise in Uosm. and a reduction in V/GFR times 100 and CH2O/GFR times 100. Although the response to VP appeared earlier than that to dibutyryl cyclic-AMP, the magnitude of the changes in Uosm., V/GFR times 100, and CH2O/GFR times 100 was eventually the same with both substances. Comparison between normal and Li+-treated rats revealed that the response to both VP and dibutyryl cyclic-AMP was blunted, albeit to a greater extent in the former. Inhibition by Li+ of adenylate cyclase will only partially explain the present data. Impairment in the release of endogenous VP or a block distal to the formation of cyclic-AMP must have played a role. In view of a normal diluting capacity and the increase in the excretion of phosphate and uric acid, it is suggested that Li+, when administered chronically in the present doses, inhibits proximal tubular reabsorption.
 ...
PMID:Renal effects of lithium administration in rats: alterations in water and electrolyte metabolism and the response to vasopressin and cyclic-adenosine monophosphate during prolonged administration. 16 79

We have previously reported systematic discrepancies between radioreceptor (RRA) and radioimmunoassay (RIA) measurements of growth hormone (hGH) in acromegalic patients. Due to limitations in RRA sensitivity, such comparisons could not be made in normal subjects. RRA methodology has now been adapted to allow detection of hGH at normal circulating levels. Since variations in Na+, K+, Ca++, and Mg++, incubation at 37 C and 4 C, and delayed tracer addition failed to improve assay sensitivity, specimen size was increased to 300 mul and incubation volume to 1.5 ml, while holding the quantity of added receptor constant. Best assay sensitivity, in room temperature incubations in 25 mM Tris for 16 h at pH 7.6 and 10 mM Ca++, was 0.66 +/- 0.30 ng hGH per ml serum. Under these conditions, 200 mug hepatic receptor protein bount 15.8 +/- 0.83% of added 125I-hGH, and 8.72 +/- 0.85% of bound tracer was displaced by 0.25 ng added unlabeled hGH. Nonspecific depression of binding by serum did not impair assay sensitivity with most receptor preparations. The basal hGH measured by RIA (antiserum 68-416) in a group of normal short children was 1.97 ng/ml, similar to the RRA result, 1.89 ng/ml (P = NS). Comparative measurements were also made in selected samples of sufficient volume during the 1 1/2 h following administration of hGH secretagogues (insulin, arginine, L-dopa). In these samples, the RIA value was 9.34 +/- 0.68 and the RRA value 6.29 +/- 0.62 ng/ml (P less than 0.01); the RIA/RRA was 1.77 +/- 0.18. Thus, no significant measurement discrepancy was found in basal samples from normal subjects, in contrast to previous findings in acromegalics. The appearance of such a discrepancy within 90 min after stimulation of hGH might be due to RIA/RRA discordance in secreted molecular subspecies, or might arise from peripheral hGH metabolism.
 ...
PMID:Radioreceptor-inactive growth hormone associated with stimulated secretion in normal subjects. 16 86

Insulin accelerates the entry of glucose and amino acids into muscle cells by acting upon the 'carrier-facilitated' transport mechanism. For glucose this process is passive and leads to equilibration of intracellular and extracellular concentrations. In heart muscle, glucose transport is a rate-limiting step for glucose uptake. During hypoxia and ischemia the heart turns to anaerobic glycolysis for energy production and therefore, maximal glucose transport becomes important. Insulin is necessary to insure proper protein synthesis, probably at the level of membrane-bound polyribosomes. However, during myocardial hypoxia, insulin alone cannot restore the associated depression in protein synthesis. Although insulin hyperpolarizes the cell, a change in the ratio of intracellular to extracellular activities of potassium is not its primary mode of action. An insulin-induced configurational change in the plasma membrane could simultaneously account for the effects of insulin on sodium and potassium permeability and the action on facilitated transport. Intracellular levels of cyclic adenylate may be reduced by insulin in adipose tissue because of inhibition of adenyl cyclase or stimulation of phosphodiesterase. However, at this time there is little evidence that insulin alters cyclic AMP levels in the heart. Insulin secretion is depressed in patients with heart disease in proportion to the reduction of cardiac index sustained. Since the ischemic heart is dependent upon glucose as the major fuel, insulin lack may deprive the heart of adequate substrate.
 ...
PMID:Insulin: fundamental mechanism of action and the heart. 18 67

This research examined the effects of several cyclic nucleotides on in vivo cat soleus nerves and muscles. The reagents were administered by rapid close intra-arterial injection while electrical activity in single motor axons and contractile activity in the whole muscle were monitored. Cyclic N6-2'-O-dibutyryl adenosine 3',5'-monophosphate (dibutyryl cAMP) initiated bursts of action potentials in unstimulated axons. It also caused the occurrence of stimulus bound repetitive potentials in stimulated axons. It caused the muscle to undergo a series of rapid asynchronous contractions and potentiated the strength of stimulus-evoked contractions. Monobutyryl cAMP produced similar responses, but was less potent than dibutyryl cAMP. cAMP produced only a small, transient depression of neuromuscular transmission. There was no response to dibutyryl cyclic 3',5' guanosine monophosphate or sodium butyrate. None of these reagents affected denervated muscle. The results suggest that cAMP-like materials that can penetrate nerve membranes cause depolarization of motor nerve terminals, prolongation of the depolarization of the terminal initiated by an action potential and release of transmitter.
 ...
PMID:Effects of cyclic nucleotides on mammalian motor nerve terminals. 18 84

Post-tetanic potentiation (PTP) of monosynaptic reflex was estimated in spinal cords in the drug-free state after the administration of a convulsant dose of penicillin and after the administration of phenytoin. There was no apparent correlation between the degree of depression of PTP and the efficacy of controlling seizure activity by phenytoin. Extracellular potassium levels were measured with ion-selective microelectrodes. The post-stimulation clearing of [K+]0 was not accelerated by phenytoin, and frequently it was slowed. Post-stimulus undershooting of [K+]0 was diminished. Oxidation of NADH in cortex and of cytochrome a, a3 in spinal cord were measured by optical methods. Stimulus-evoked transient oxidation responses evoked by electrical stimulation were depressed by phenytoin. It is concluded that systemic administration of phenytoin in therapeutic doses does not stimulate Na+-K+-activated membrane ATPase in cortex and spinal cord. Unlike other depressants, phenytoin did not cause a reduction of "resting" redox levels of respiratory enzymes. The local regulation of blood flow remained unaltered after phenytoin administration. Phenytoin caused a moderate but consistent depression of the stimulus-evoked responses of potassium activity, electric potential, and oxidative enzymes, consistent with diminished outflow of potassium from cells, owing either to lesser activation of cells or to a lesser exchange of ions.
 ...
PMID:Phenytoin, electric, ionic, and metabolic responses in cortex and spinal cord. 19 41


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