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)

The effect of glucose on alanine-stimulated urea synthesis was studied in six healthy volunteers during 6 h of constant alanine infusion, 2.8 mmol h-1 kg-1 b. wht., and during 12 h of constant glucose infusion, 4.0 mmol h-1 kg-1 b. wht., with superimposed alanine infusion. The urea nitrogen synthesis rate (UNSR) was determined at intervals of 2 h as urinary excretion rate corrected for accumulation and intestinal hydrolysis. UNSR depended on the blood alanine and glucagon concentration, but was not correlated with glucose, lactate, or insulin concentrations. The slope of the linear relation between UNSR and alanine concentration (the 'Functional Hepatic Nitrogen Clearance') was on the average 24.4 1 h-1 and decreased to 12.8 1 h-1 by glucose (mean difference +/- SE of the difference 10.6 +/- 7.3, P less than 0.01). The relation between glucagon and alanine concentration was linear, and the slope was decreased to 40 per cent by glucose (P less than 0.05). The slope of the linear relation between UNSR and glucagon was not changed by glucose. Thus the catabolism of alanine nitrogen is decreased by glucose because of a reduction of the urea synthesis. Data suggest that this may be due to a depression of the glucagon response to alanine.
 ...
PMID:Effects of glucose on alanine-derived urea synthesis. 654 35

Rats fed a purified L-amino acid diet with 0.72, 1.50, 2.9 or 4.3% lysine excreted 117, 124, 237 and 628 micrograms/day orotic acid, respectively. Dietary arginine supplementation prevented the orotic aciduria induced by excess dietary lysine. Increased orotic acid excretion was accompanied by a significant depression in urinary urea in rats fed a diet containing 4.3% lysine compared to those fed a diet containing 0.72% lysine. As measured by incorporation of [14C]HCO3, lysine addition to liver slices or isolated hepatocytes resulted in a progressive increase in the rate of orotic acid biosynthesis. The minimum quantity of lysine tested that significantly increased the rate of orotic acid biosynthesis was 0.5 mM or 1 mM for studies with slices and hepatocytes, respectively. Ammonia at concentrations of 0, 0.75, or 5.0 mM NH4Cl linearly increased orotate and urea synthesis. Inhibition of urea biosynthesis resulting from lysine supplementation coincided with an increase in pyrimidine biosynthesis. Addition of 1 mM arginine to the liver incubation media prevented the increased rate of orotic acid biosynthesis caused by lysine. Arginine addition may overcome an approximate 90% competitive inhibition of arginase by excess lysine.
 ...
PMID:The influence of excess lysine on urea cycle operation and pyrimidine biosynthesis. 681 6

By evaluating the ability of endotoxin to prevent hyperoxic depressions in lung amine uptake, this study assessed whether bacterial endotoxin protects against hyperoxic injury to the pulmonary endothelium. Rats were given 500 or 1,500 micrograms/kg body wt of endotoxin or saline (controls) 30 min before a 24-h or 7-day exposure to air or 100% O2 at 1 ATA. Immediately after exposure, lungs were isolated, ventilated, and perfused via the pulmonary artery and the uptake of two amines, [14C] serotonin and [3H]norepinephrine, was measured. Amine uptake by the lungs of control rats exposed to 100% O2 for 24 h was significantly depressed, whereas amine uptake by the lungs of endotoxin-treated rats exposed to 100% O2 for 24 h was comparable to that in air-exposed controls. Endotoxin also prevented hyperoxic depression of lung amine uptake and prolonged survival in rats exposed to 100% O2 for 7 days. Pretreatment of rats with endotoxin protects against hyperoxic injury to the pulmonary endothelium, which may account for the reduced mortality in endotoxin-treated animals.
 ...
PMID:Endotoxin protects against hyperoxic alterations in lung endothelial cell metabolism. 682 8

The amino acid and ammonia profiles in various tissues of the rat exposed to different pressures of pure oxygen have been studied. Well-defined changes in behavioral activity accompanied a profile of increasing pressure, culminating in convulsive activity in each group of exposed animals. After an initial depression of ammonia, in all tissues studied at 0.68 atm oxygen ammonia increased significantly at higher oxygen pressures. A rise in tissue ammonia took place in the absence of undue muscular activity on the part of the exposed animals. A significant increase in ammonia occurred first in brain and liver at 3.40 atm. Ammonia concentration was high in all tissues after convulsions occurred at 4.08 atm. Between 0.68 and 2.72 atm oxygen, tissue ammonia concentration was generally low and brain glutamate and gamma-aminobutyric acid were high. At pressures higher than 2.72 atm oxygen, tissue glutamate declined and glutamine increased. Alanine became significantly elevated in serum and muscle at high oxygen pressure, and aspartate was depressed in heart, liver, and muscle. These pressure-course experiments on ammonia accumulation in tissue confirm previous serial time course observations that ammonia accumulates in the brain and several tissues of the rat even in the absence of undue muscular activity during high-pressure oxygen exposure and is a significant factor in inducing convulsions.
 ...
PMID:Tissue ammonia and amino acids in rats at various oxygen pressures. 683 41

Intracellular recordings from CA1 pyramidal cells in the rat hippocampal slice preparation have been used to study the action of ammonia on inhibitory postsynaptic potentials (IPSPs). Concentrations of ammonia less than 2 mM had little effect on IPSPs or the action of iontophoretically applied gamma-aminobutyric acid (GABA). This concentration has been reported to be fully effective in blocking hyperpolarizing IPSPs in spinal cord and neocortex. Concentrations above 2 mM did cause a depolarizing shift in the IPSP and GABA reversal potentials, but this effect was accompanied by several generalized effects. The conductance increase during the IPSP but not during the GABA response was depressed, indicating that ammonia has a presynaptic depressant effect on the IPSP. Ammonia also depressed excitatory postsynaptic potentials (EPSPs), presynaptic fiber potentials, and pyramidal cell population spikes. In addition, the calcium-dependent potassium response elicited by depolarizing current pulses was depressed. This depression was due, in part, to a depolarizing shift in the reversal potential for this response. Responses recorded with potassium-sensitive microelectrodes indicate that ammonia releases potassium into the extracellular space. The possibility is discussed that the shifts in IPSP reversal potential seen with high concentrations of ammonia are a consequence of generalized nonspecific effects. We conclude that the relative insensitivity of hippocampal IPSPs to blockade by ammonia suggests that a mechanism fundamentally unlike an ammonia-sensitive chloride pump must maintain the hippocampal IPSP gradient.
 ...
PMID:Ammonia does not selectively block IPSPs in rat hippocampal pyramidal cells. 687 29

The activity of a selective cholecystokinin (CCK)-A receptor agonist, N-acetyl derivative of A71623 (Ac-Trp-Lys(epsilon-N-[2-methylphenylamino-carbonyl]) -Asp-(NMe)Phe-NH2) was investigated in the guinea pig isolated ileum longitudinal muscle myenteric plexus. NAA caused both a phasic and tonic contraction at all concentrations tested (1-1000 nM). The selective CCK-A antagonist L-364,718 (Devazepide) antagonized both types of contraction with a pKB of 10.10 and 9.95, respectively. The CCK-B selective antagonist L-365,260 ((3R(+)-2,3-dihydro-1-methyl-2-oxo-5-phenyl-1H-1, 4-benzodiazepine-3yl)-N-(3-methylphenyl)-urea) was inactive up to a concentration of 30 nM. Atropine at 300 nM and 1000 nM reduced the maximal response of NAA by only 17% and 50%, respectively. The selective neurokinin (NK)-1 antagonists GR 82334 ([D-pro9[Spiro-gamma-Lactam] Leu10, Trp11]-Phys (1-11)9) at 300 and 1000 nM and (+-) CP-96,345 [(2S, 3S)-cis- 2-(diphenylmethyl)-N- [(2-methoxyphenyl)-methyl] -1-azabici-clo [2.2.2]octan-3-amine] at 10 nM were inactive or partially active. When atropine and GR 82334 or (+/-) CP-96,345 were combined, they produced a dose-dependent synergistic inhibition of both phasic and tonic contractions induced by NAA. The selective NK-3 receptor agonist senktide induced both phasic and tonic contractions that were blocked by tetrodotoxin. In the presence of atropine and GR 82334, both 300 nM, a synergistic depression of the response to senktide similar to that observed for the agonist NAA was disclosed.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:A further analysis of the contraction induced by activation of cholecystokinin A receptors in guinea pig isolated ileum longitudinal muscle-myenteric plexus. 752 Sep 41

Effects of atmospheric ammonia (NH3) on the nasal mucosa and somatic growth were investigated in pigs exposed to 4 NH3 concentrations (0; 25; 50; and 100 ppm) for 6 days in a specifically designed air-pollutant exposure chamber. Nasal lavage (NAL) was applied to quantify the ammonia-induced inflammatory response by measuring the number of neutrophils and the albumin (porcine serum albumin) concentration in the NAL liquid. In control pigs, these variables remained unchanged throughout the exposure period. In all other groups, an important ammonia concentration-related increase was recorded. The equation of the linear regression line established between the mean values of the number of neutrophils (x 10(3)) per milliliter of NAL liquid (y) recorded at the end of the exposure period and the ammonia concentrations (ppm) was: y = 69.7 + 3.3 [NH3] (r = 0.979; P < 0.020). The increase in the neutrophil count was significant (P < 0.05) at concentrations as low as 25 ppm. For albumin concentration nanograms per milliliter, the corresponding equation was: y = 574 + 14.3 [NH3] (r = 0.953; P < 0.045). However, the first significant change (P < 0.05) in this variable was only obtained for the higher concentration (100 ppm). In exposed pigs, a concentration-related depression of somatic growth was observed. The equation of the regression line plotted relating the individual values of the changes in body weight gain recorded over the exposure period expressed as percentage of the initial body weight (y) and the ammonia concentration was: y = 3.507-0.203 [NH3] + 0.001 [NH3]2 (r = 0.55; P < 0.010).(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Quantitative assessment of aerial ammonia toxicity to the nasal mucosa by use of the nasal lavage method in pigs. 780 5

Selective CCKA and CCKB receptor agonists and antagonists were used to study the involvement of endogenous cholecystokinin in the behavioural changes that occur in mice in the forced-swimming test (Porsolt's test). The CCKB receptor antagonist, L-365,260 ((3R)-(+)-N-(2,3-dihydro-1-methyl-2-oxo-5-phenyl-1H-1,4- benzodiazepin-3-yl)-3-methylphenylurea), but not the CCKA receptor antagonist, devazepide ((3S)-(-)-N-(2,3-dihydro-1-methyl-2-oxo-5-phenyl-1H-1,4-benzodiazepin -3-yl)- 1H-indole-2-carboxamide), elicited an antidepressant-type response (a decrease in the duration of immobility) that was suppressed by previous treatment with either CCK-8 (H-Asp-Tyr(OSO3H)-Met-Gly- Trp-Met-Asp-Phe-NH2) or the selective CCKB receptor agonist BC-264 (Boc-Tyr(SO3H)-gNle-mGly-Trp-N(Me)-Nle-Asp-Phe- NH2). The L-365,260 effect was also prevented by the dopamine receptor antagonist, SCH-23,390 (a dopamine D1-selective receptor antagonist: R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl- 2,3,4,5-tetrahydro-1H-3-benzazepine) and sulpiride (a dopamine D2-selective receptor antagonist: (-)-5-(aminosulfonyl)-N-[(1-ethyl-2-pyrrolidinyl) methyl]-2-metoxybenzamide). On the other hand, co-administration of subthreshold doses of L-365,260 and nomifensine (an atypical antidepressant that selectively blocks dopamine re-uptake mechanisms, 1,2,3,4-tetrahydro-2-methyl-4-phenyl-8-isoquinolinamine) led to a potent antidepressant-type response. These results indicate that blocking of CCKB receptors could result in an increase of extracellular dopamine contents in some brain areas involved in depression and suggest a potential use of CCKB receptor antagonists, alone or combined with antidepressants, in the treatment of depressive syndromes.
 ...
PMID:The CCKB receptor antagonist, L-365,260, elicits antidepressant-type effects in the forced-swim test in mice. 781 46

Opium and its derivatives are potent analgesics that can also induce severe side effects, including respiratory depression and addiction. Opioids exert their diverse physiological effects through specific membrane-bound receptors. Three major types of opioid receptors have been described, termed delta, kappa, and mu. The recent molecular cloning of these receptor types opens up the possibility to identify the ligand-binding domains of these receptors. To identify the ligand-binding domains of the kappa and delta receptors, we have expressed in COS-7 cells the cloned mouse delta and kappa receptors and chimeric delta/kappa and kappa/delta receptors in which the NH2 termini have been exchanged. The opioid antagonist naloxone binds potently to wild-type kappa receptor but not to wild-type delta receptor. The kappa/delta chimera bound [3H]naloxone with high affinity. In contrast, the kappa-specific agonist [3H]U-69,593 did not bind to the kappa/delta chimera. These findings indicate that selective agonists and antagonists interact with different recognition sites in the kappa receptor and localize the antagonist-binding domain to the NH2 terminus. Consistent with the results of radioligand-binding studies, the kappa/delta chimera did not mediate kappa-agonist inhibition of cAMP formation. In contrast, the delta/kappa chimera did mediate kappa-agonist inhibition of cAMP formation, but this effect was not blocked by naloxone. Furthermore, a truncated kappa receptor lacking its NH2 terminus was able to mediate agonist inhibition of cAMP accumulation in a naloxone-insensitive manner. This result further indicates that the NH2 terminus of the kappa receptor contains the selective antagonist-binding domain. The ability to dissociate agonist- and antagonist-binding sites will facilitate the development of more specific kappa agonists, which could have analgesic properties devoid of side effects.
 ...
PMID:Agonists and antagonists bind to different domains of the cloned kappa opioid receptor. 805 54

An inverse relation is known to link blood potassium with renal synthesis and the release of ammonia. Given the liability of hyperammonemia for precipitating hepatic encephalopathy (HE), 28 patients affected by stage I HE were equally divided into two groups and maintained up to their death at the highest (5.4-5.5 mEq/l) or the lowest (3.5-3.6 mEq/l) normokalemia levels. When compared with the lowest normokalemia group, the highest one showed an early, albeit transient, improvement in the mental state (as assessed by both EEG and psychiatric investigations) and to a lesser extent in hepatic functions (as assessed by the variations in serum bilirubin, GPT, GGT and plasma prothrombin time). In the highest normokalemia group the survival was also prolonged. The cause of this improvement may be related to the induced decrease in blood pH, the consequent depression of renal ammoniagenesis and the rise in the arterial and urine NH+4/NH3 ratios. These factors reduce the entry of ammonia into the cells and enhance the urinary excretion of this metabolite, respectively.
 ...
PMID:The importance of the highest normokalemia in the treatment of early hepatic encephalopathy. 816 17


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