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)

Reaction conditions are described that permit the enzyme-assisted semi-synthetic replacement of residue B30 of pig insulin (or of analogue) to proceed in very high yield in 2 h or less. Immobilized trypsin may be used as catalyst, and excess amino acid ester may be recycled after a simple extraction. Alanine-B30 may be replaced by a variety of nucleophiles, including threonine O-t-butyl ether t-butyl ester, in which case the yield of crude product is about 99%. De-protection of the B30 threonyl ester analogue of insulin thus formed then affords human insulin in an overall yield of about 92%, based on pig starting material. The product has full biological potency, as determined by depression of blood glucose concentration in rats, and showed the expected behaviour on radioimmunoassay.
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PMID:Rapid preparation of human insulin and insulin analogues in high yield by enzyme-assisted semi-synthesis. 634 13

The potential immunosuppressive drug beta-[1-Phenyl-5-bis(beta-chloroethyl-5-amino-benzimidazolyl-(2)]-DL-alanine (ZIMET 3164) was tested for its effect on cell-mediated immunity. The models "skin grafting" and "contact hypersensitivity" were used. --The results showed a marked prolongation of the mean survival time of the skin grafts and also a high depression of the contact hypersensitivity (delayed hypersensitivity) to picryl chloride. The immunosuppressive efficacy of ZIMET 3164 was higher than that of the reference compound cyclophosphamide.
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PMID:The immunosuppressive effect of beta-[1-phenyl-5-bis(beta-chloroethyl)-aminobenzimidazolyl-(2)]-DL-alanine (ZIMET 3164) on cell-mediated immunity in mice. 644 47

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.
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PMID:Effects of glucose on alanine-derived urea synthesis. 654 35

Thirty-two pairs (n = 64) of Mongolian gerbils were surface cooled to 18 degrees C and randomly subjected to 0 to 180 minutes of bilateral carotid occlusion in the neck. They were rewarmed after release of the carotid occlusion. After rewarming, one member of each pair was allowed to survive 7 days and then was put to death for brain histologic study; the other was subjected to brain preservation by quick freezing for subsequent biochemical studies. In the survivors, neurologic function was depressed during the 7 subsequent days, and the depression was in direct relation to the time of carotid occlusion (p = 0.0005). The proportion of normal hippocampal neurons decreased in direct proportion to the length of carotid occlusion (p less than 0.0001). The depression in neurologic function and in the proportion of normal neurons was evident when occlusion time exceeded 45 minutes. The proportion of normal neurons was correlated with neurologic function (r = 0.56, p = 0.0001). Cortical adenosine triphosphate (ATP) concentration after brain reperfusion was reduced in comparison with normal and varied inversely with carotid occlusion time (r = -0.84, p less than 0.0001). Alanine (p less than 0.001), lactate (p = 0.01), and pyruvate (p = 0.001) concentrations were elevated, in direct relation to carotid occlusion time. These observations are consistent with other experimental studies of profoundly hypothermic total circulatory arrest and indicate the damaging effect of this modality, particularly when the circulatory arrest time exceeds 45 minutes.
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PMID:The effect of hypothermic circulatory arrest time on cerebral function, morphology, and biochemistry. An experimental study. 663 51

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.
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PMID:Tissue ammonia and amino acids in rats at various oxygen pressures. 683 41

Resistance to insulin-mediated glucose uptake is well documented in uremia. We have previously reported that in vivo resistance to insulin mediated amino acid uptake is present in the skeletal muscle of acutely uremic rats. This report compares the effect of insulin on in vitro 14C alpha-amino isobutyric acid and cycloleucine uptake by skeletal muscle from uremic and control rats. Intracellular accumulation of 14C alpha-amino isobutyric acid were normal in the diaphragm and epitrochlear muscle of acutely uremic rats in the absence of insulin. However, insulin failed to further stimulate amino acid uptake in both tissues. Insulin also failed to stimulate cellular uptake of cycloleucine in skeletal muscle from acutely uremic animals. Resistance to insulin-mediated amino acid uptake was evident in rats with chronic uremia. This resistance to insulin mediated increases in intracellular amino acid concentration may contribute to the abnormal depression in protein synthesis or the exaggerated gluconeogenesis and alanine turnover seen in uremia.
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PMID:In vitro suppression of insulin-mediated amino acid uptake in uremic skeletal muscle. 699 70

To test the effects of acute cold on muscle amino acid and protein 1) rats were exposed to 4 degrees C for 24 h, functionally hepatectomized (eviscerated) and accumulation in the blood used to indicate changes in amino acid release from the tissues; 2) other rats were left intact, and urinary excretion of 3-methylhistidine (proportional to muscle protein breakdown) determined during cold exposure. In the eviscerated group, cold enhanced loss of total amino acids from the tissues (as alpha-amino nitrogen), but the loss (213 +/- 14.8% of basal in 2 h) was not due to excess alanine (180 +/- 8.5%). By comparison, in fasted rats total amino acid was 182 +/- 12.3, alanine 309 +/- 17.2%. Also, the cold-induced loss resembled the effects of streptozotocin diabetes and depended on a depression by cold of serum insulin (to 35.7 +/- 2.3 muU/ml). Therefore it was prevented when insulin was restored by infusion (40 mU . 100 g-1 . h-1) or by adrenodemedullation before cold exposure. Epinephrine (10 micrograms/100 g sc) depressed insulin in the latter and permitted amino acid release to recur. In intact rats, 3-methylhistidine excretion was unaffected by cold. The results suggest that although cold fails to stimulate alanine synthesis or protein breakdown, it inhibits insulin release sympathetically, thereby diminishing the amount of amino acid incorporated into muscle protein.
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PMID:Effects of acute cold exposure on muscle amino acid and protein in rats. 704 71

Many polar fishes synthesize a group of eight glycopeptides that exhibit a non-colligative lowering of the freezing point of water. These glycopeptides range in molecular weight between 2600 and 33 700. The largest glycopeptides [1-5] lower the freezing point more than the small ones on a weight basis and contain only two amino acids, alanine and threonine, with the disaccharide galactose-N-acetyl-galactosamine attached to threonine. The small glycopeptides, 6, 7, and 8, also lower the freezing point and contain proline, which periodically substitutes for alanine. Glycopeptides with similar antifreeze properties isolated from the saffron cod and the Atlantic tomcod contain an additional amino acid, arginine, which substitutes for threonine in glycopeptide 6. In this study we address the question of whether differences in amino acid composition or molecular weight between large and small glycopeptides are responsible for the reduced freezing point depressing capability of the low molecular weight glycopeptides. The results indicate that the degree of amino acid substitutions that occur in glycopeptides 6-8 do not have a significant effect on the unusual freezing point lowering and that the observed decrease in freezing point depression with smaller glycopeptides can be accounted for on the basis of molecular weight.
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PMID:Relationship of amino acid composition and molecular weight of antifreeze glycopeptides to non-colligative freezing point depression. 711 72

The synthetic opiate D-Alanine-methionine enkephalin (D-Ala) affects neuronal activity of the fascia dentata (FD). D-Ala causes a depression of the population spike evoked by stimulation of the perforant path, which is antagonized by naloxone. In so called "Tandem" experiments it was shown that D-Ala had opposite effects on the CA1 pyramidal and FD granule cells. It is likely that in the FD the site of action of D-Ala is at the afferent synapses.
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PMID:Differential effects of enkephalin within hippocampal areas. 730 49

1. The aim of this study was the pharmacological characterization of tachykinin NK1 and NK2 receptors mediating contraction in the circular muscle of the guinea-pig ileum and proximal colon. The action of substance P (SP), neurokinin A (NKA) and of the synthetic agonists [Sar9]SP sulphone, [Glp6,Pro9]SP(6-11) (septide) and [beta Ala8]NKA(4-10) was investigated. The affinities of various peptide and nonpeptide antagonists for the NK1 and NK2 receptor was estimated by use of receptor selective agonists. 2. The natural agonists, SP and NKA, produced concentration-dependent contraction in both preparations. EC50 values were 100 pM and 5 nM for SP, 1.2 nM and 19 nM for NKA in the ileum and colon, respectively. The action of SP and NKA was not significantly modified by peptidase inhibitors (bestatin, captopril and thiorphan, 1 microM each). 3. Synthetic NK1 and NK2 receptor agonists produced concentration-dependent contraction of the circular muscle of the ileum and proximal colon. EC50 values were 83 pM, 36 pM and 10 nM in the ileum, 8 nM, 0.7 nM and 12 nM in the colon for [Sar9]SP sulphone, septide and [beta Ala8]NKA-(4-10), respectively. The pseudopeptide derivative of NKA(4-10), MDL 28,564 behaved as a full or near-to-full agonist in both preparations, its EC50s being 474 nM and 55 nM in the ileum and colon, respectively. 4. Nifedipine (1 microM) abolished the response to septide and [Sar9]SP sulphone in the ileum and produced a rightward shift and large depression of the response in the colon. The response to [beta Ala8]NKA(4-10) was abolished in the ileum and largely unaffected in the colon. 5. The NK1 receptor antagonists, (+/-)-CP 96,34, FK 888 and GR 82,334 competitively antagonized the response to septide and [Sar9]SP sulphone in both preparations without affecting that to [beta Ala8]NKA(4-10). In general, the NK1 receptor antagonists were significantly more potent toward septide than [Sar9]SP sulphone in both preparations. 6. The NK2 receptor antagonists, GR 94,800 and SR 48,968 selectively antagonized the response to [beta Ala8]NKA(4-10) without affecting that to [Sar9]SP sulphone or septide in the ileum and colon. SR 48,968 produced noncompetitive antagonism of the response to the NK2 receptor agonist in the ileum and competitive antagonism in the colon. 7. MEN 10,376 and the cyclic pseudopeptide MEN 10,573 antagonized in a competitive manner the response to [beta Ala8]NKA(4-10) in the ileum and colon. While MEN 10,573 was equipotent in both preparations, MEN 10,376 was significantly more potent in the colon than in the ileum. MEN 10,376was also effective against septide in both preparations, without affecting the response to [Sar9] SP sulphone. MEN 10,573 antagonized the response to [Sar9]SP sulphone and septide in both preparations,pKB values against septide being intermediate, and significantly different from, those measured against[Beta Ala 8]NKA(4-10) and [Sa9]lSP sulphone.8. These findings show that tachykinin NK1 and NK2 receptors mediate contraction of the circular muscle of the guinea-pig ileum and colon. In both preparations NK1 receptor antagonists display higher apparent affinity when tested against septide than [Sar9]SP sulphone. These findings are compatible with the proposed existence of NK1 receptor subtypes in guinea-pig, although alternative explanations (e.g.agonist binding to different epitopes of the same receptor protein) cannot be excluded at present.Furthermore, an intraspecies heterogeneity of the NK2 receptor in the circular muscle of the guinea-pig ileum and colon is suggested.
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PMID:Comparison of tachykinin NK1 and NK2 receptors in the circular muscle of the guinea-pig ileum and proximal colon. 751 2


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