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)

Metalloendoprotease activity that was sensitive to the metal chelator 1,10-phenanthroline and to synthetic dipeptide substrates of the enzyme was detected in homogenates of dorsal root ganglia (DRG) and spinal nerve from the bullfrog. Exposure of an intact in vitro preparation of DRG and spinal nerves to 1,10-phenanthroline led to a dose-dependent depression in the accumulation of fast-transported 3H-labeled protein proximal to a nerve ligature. In nonligated preparations, the chelator treatment reduced the amount of transported protein entering the nerve; no marked effect on the transport rate was observed. Exposure of a desheathed region of spinal nerve to 1,10-phenanthroline, while DRG were maintained in control medium, resulted in a slight depression of fast transport. This effect was not dose dependent over the range that produced a dose response when both DRG and spinal nerve were exposed to the drug. Treatment of DRG and spinal nerve with the metalloendoprotease substrate analogues carbobenzoxy (CBZ)-Ser-Leu-amide or CBZ-Gly-Leu-amide inhibited fast axonal transport, whereas treatment with CBZ-Gly-Gly-amide, which is not a substrate, had no detectable effect on transport. Selective exposure of desheathed nerve trunk to CBZ-Ser-Leu-amide inhibited fast transport, but the effect was less marked than when DRG and nerve trunk were treated. Although previous studies have focused on the role of metalloendoprotease activity in exocytosis, the present data suggest that the enzyme may also be involved in earlier stages of intracellular transport.
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PMID:Metalloendoprotease inhibitors block fast axonal transport. 278 54

The effect of leucine enkephalin (LNK) on spontaneous locomotor activity was studied in mice of both sexes. The effect of a depressant dose of ethanol (ET) on LNK-mediated response on motility was also studied. In addition, the determination of specific activities of the hepatic enzymes primarily involved in the metabolism of ET and acetaldehyde was studied. Lactate dehydrogenase (LDH) isoenzymes were also assayed in both plasma and heart tissues. Intraperitoneal injection of LNK, 100 mg/kg, exerted behavioral depression in the male but not female mouse compared to controls. This effect was apparent for the initial 30 min posttreatment. Injection of two smaller doses of LNK, which were devoid of effect on mouse motility, prior to a depressant dose of ET counteracted ET-caused depression of motility only in the female mouse. This became apparent 30 min postdrug injection and lasted for 60 min thereafter. The LNK and ET treatment inhibited only male mouse liver aldehyde dehydrogenase in both cytoplasmic and mitochondrial preparations concomitant with reduction of plasma but not heart LDH1 isoenzyme from corresponding controls. The results suggest that LNK and ET affect different systems involved in behavioral depression tested and show a potential for LNK in antagonizing the ET effect studied. The data also indicate a sex-dependent effect of LNK on motility and of its interaction with ethanol on the enzymes studied.
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PMID:Effect of leucine enkephalin on ethanol produced behavioral depression in the mouse. 281 53

Clostridium perfringens enterotoxin binds to receptors on Vero cells. This process does not depend on the presence of divalent cations (Ca++, Mg++). Binding of enterotoxin causes inhibition of 14C-leucine incorporation into proteins, probably because of depression of amino acid transport. The presence of Mg++ speeds up this effect of the enterotoxin. The enterotoxin produces membrane leakage only in the presence of Ca++, but additional Mg++ increases the rate of this process. These results indicate that the dissociation constant of the enterotoxin receptor interaction is reduced in the presence of Mg++. A model for the mode of action of the enterotoxin is proposed.
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PMID:The effect of Ca++ and Mg++ on the action of Clostridium perfringens enterotoxin on Vero cells. 285 53

The effects of selective opioid receptor agonists and antagonists on neural discharge recorded from carotid body arterial chemoreceptors in vivo were studied in anaesthetized cats. Mean ID50 values were determined for each agonist and used to assess chemodepressant potency on intracarotid (i.c.) injection in animals artificially ventilated with air. [Met]enkephalin, [Leu]enkephalin, [D-Ala2, D-Leu5]enkephalin and [D-Pen2, D-Pen5]enkephalin were more potent chemodepressants than [D-Ala2, Me-Phe4, Gly-ol5]enkephalin, dynorphin (1-8) or ethylketocyclazocine; morphiceptin (mu-agonist) was inactive. The rank order of potency was compatible with the involvement of delta-opioid receptors in opioid-induced depression of chemosensory discharge. ICI 154129, a delta-opioid receptor antagonist, was used in fairly high doses and caused reversible dose-related antagonism of chemodepression induced by [Met]enkephalin. It also antagonized depression caused by single doses of [Leu]enkephalin, [D-Ala2, D-Leu5]enkephalin, [D-Ala2, Me-Phe4, Gly-ol5]enkephalin or dynorphin (1-8). ICI 174864, a more potent and selective delta-opioid receptor antagonist, also antagonized chemodepression induced by [Met]enkephalin or by the selective delta-receptor agonist [D-Pen2, D-Pen5]enkephalin. Comparison of background or 'spontaneous' chemosensory discharge during the 30 min periods immediately before and after injecting ICI 174864 (0.1-0.2 mg kg-1 i.c.) showed a significant increase in discharge in one experiment, but in four others discharge was either unaffected or decreased after the antagonist, which argues against a toxic depression of chemosensors by endogenous opioids under resting conditions in our preparation. Sensitivity of the carotid chemoreceptors to hypoxia (ventilating with 10% O2) was increased significantly after ICI 174864, which could be taken as evidence that endogenous opioids depress chemosensitivity during hypoxia. In contrast, responsiveness to hypercapnia was reduced after the antagonist, implying that endogenous opioids may potentiate chemoreceptor sensitivity during hypercapnia. The results obtained using 'selective' agonists and antagonists provide evidence that depression of chemosensory discharge caused by injected opioids involves a delta type of opioid receptor within the cat carotid body. Endogenous opioids may modulate arterial chemoreceptor sensitivity to physiological stimuli such as hypoxia and hypercapnia.
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PMID:Characterization of opioid receptors in the cat carotid body involved in chemosensory depression in vivo. 287 62

Polymorphonuclear leukocytes (PMN) form a major part of the body's nonspecific first line of defense. An early event, prerequisite for the effective restriction of microbial invasions, is the chemotactic movement of activated neutrophils towards the invading organisms. To date, only limited and contradictory data exist regarding the effects of various intravenous anesthetic agents on neutrophil migration. In this study, the influence of ketamine, etomidate, midazolam, diazepam, and six commonly used i.v. barbiturates (hexo-, pheno-, pentobarbital, methohexital, thiopental, thiobutobarbital) on the in vitro motility of isolated human PMN was tested. Purified PMN (greater than 95%) were obtained from venous blood samples of healthy adults by dextran sedimentation, subsequent ammonium chloride treatment for red blood cell lysis, and Ficoll-Hypaque gradient centrifugation. Random and chemotactic migration were assessed under 1% agarose in the presence of 10(-3)-10(-7) M logarithmic dilutions of the agents in antibiotic free migration medium (MEM). N-fMet-Leu-Phe (FMLP) served as the standardized chemical attractant (10(-7) M). PMN motility was unaffected by ketamine and etomidate, but a significant (P less than 0.001), dose - related depression could be observed with both benzodiazepines at concentrations exceeding 10(-5) M (Fig. 1). Except at 10(-3) M concentration, this migratory inhibition proved to be easily reversible (Fig. 3). At the highest concentration tested (10(-3) M), all the barbiturates caused a significant (P less than 0.001) but completely reversible depression of random as well as chemotactic PMN migration (Table 1).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Intravenous anesthetics and human neutrophil granulocyte motility in vitro]. 288 93

We have examined the sites phosphorylated on acetyl-CoA carboxylase by three protein kinases which have been shown to inactivate the enzyme, i.e. cyclic-AMP-dependent protein kinase, acetyl-CoA carboxylase kinase-2 (ACK2, purified from rat mammary gland) and the AMP-activated protein kinase (formerly called acetyl-CoA carboxylase kinase-3, purified from rat liver). Each protein kinase phosphorylates two out of three sites (termed 1-3) which have been established by amino acid sequencing. The two sites phosphorylated by each kinase can be recovered on separate peptides, TC1 and TC2, derived by combined digestion of the native enzyme by trypsin and chymotrypsin: TC1 = Ser-2Ser(P)-Met-3Ser(P)-Gly-Leu; TC2 = Arg-Met-1Ser(P)-Phe- Cyclic-AMP-dependent protein kinase phosphorylates sites 1 and 2 exclusively, whereas the AMP-activated protein kinase phosphorylates sites 1 and 3, plus at least one other minor site. ACK2 phosphorylates site 1 and, more slowly, an unidentified site(s) within TC1. We have also established the structures of the single major phosphopeptides (T1 and C1 respectively) which are recovered by HPLC after acetyl-CoA carboxylase phosphorylated by cyclic-AMP-dependent protein kinase is digested with trypsin or chymotrypsin alone. T1 is related to TC1, and has the structure: Ser-Ser(P)-Met-Ser-Gly-Leu-His-Leu-Val-Lys. C1 is identical with TC2. We have carried out studies on the correlation of the activity of acetyl-CoA carboxylase with the occupancy of sites 1, 2 and 3 during phosphorylation by each of the three protein kinases. The results suggest that phosphorylation of site 3 is primarily responsible for the large decrease in Vmax produced by the AMP-activated protein kinase, while phosphorylation of site 1 may be primarily responsible for the increase in A0.5 for citrate and more modest depression of Vmax produced by cyclic-AMP-dependent protein kinase and ACK2. Our results emphasize that amino acid sequence information is essential in the unequivocal interpretation of data from phosphopeptide mapping experiments and allow a more complete interpretation of previous data on phosphorylation of acetyl-CoA carboxylase in intact cells. They also open the way to experiments which could establish the physiological roles of these protein kinases in the control of fatty acid synthesis.
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PMID:Identification by amino acid sequencing of three major regulatory phosphorylation sites on rat acetyl-CoA carboxylase. 290 Jan 38

Previous studies in rodents have shown that ultraviolet radiation (UVR) may have direct effects on the immune system in the skin and at higher doses may induce systemic suppression of immune responses. We have previously shown that UVR from sun or solarium beds may induce systemic effects in human subjects. The purpose of the present study was to examine whether these systemic effects in human subjects could be prevented by use of commercially available sunscreen agents. Groups of 12 normal subjects were exposed to radiation from solarium lamps after application of a sunscreen agent or the base used in its preparation. Twelve half-hourly exposures induced a depression of natural killer (NK) cell activity against a melanoma and the K562 target cell which was not prevented by use of the sunscreen agent. Changes in functional activity were accompanied by a reduction in NK cell numbers assessed by Leu-11 monoclonal antibodies against the labile Fc receptor. Application of the sunscreen agent also did not protect against effects of solarium exposure on recall antigen skin tests and immunoglobulin production in vitro in pokeweed mitogen-stimulated cultures of B and T cells. These results suggest that further evaluation of the wave-length spectrum of UVR and the effectiveness of sunscreen agents in prevention of UVR-induced effects on the immune system is needed.
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PMID:Analysis of the effect of a sunscreen agent on the suppression of natural killer cell activity induced in human subjects by radiation from solarium lamps. 295 Jan 79

Experiments were undertaken to determine whether the depression of natural killer (NK) activity previously observed in the peripheral blood lymphocytes (PBL) of leukaemia patients in remission extended to NK-like precursors in the blood. T-lymphocytes (E+) from leukaemia patients and normal subjects were depleted of IgG Fc-receptor-bearing (gamma FcR) fresh NK cells by passage over immune complex-coated monolayers. gamma FcR - E + PBL were cultured alone or with DAUDI cells. On day 5 of culture, cytotoxicity toward the NK-sensitive cell lines K562 and MOLT-4 was evaluated in the responder lymphocytes of leukaemia patients and controls. Negligible NK-like cytotoxicity was found in both FcR - E + PBL responder populations cultured alone. By contrast, stimulation with DAUDI induced high levels of K562 and MOLT-4 cytotoxicity in leukaemia as well as in normal responder cells. Complement-mediated cytotoxicity experiments using various McAb demonstrated that in both normal and leukaemia cultures NK-like effectors react with the pan-T OKT3 McAb and with the OKT11 McAB directed to the SRBC receptor, but not with Leu 1 1b and OKM1 McAbs, directed against antigens expressed on peripheral blood NK cells. Fractionation of the responder cells on discontinuous Percoll gradients showed that most of this activity was present in the highly dividing blast cell fraction.
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PMID:Generation of non MHC restricted killing in non-cytotoxic T-lymphocytes from leukaemia patients. 295 Sep 19

Young rats were fed a niacin-deficient diet with and without 15 g/kg supplementary L-leucine. Both groups grew slowly for 5 wk and showed no difference in the severity of their condition. Nor did their 14CO2 production differ after intraperitoneal dosing with [methylene-14C]tryptophan. In a 2 X 3 X 3 multifactorial trial with a niacin-free basal diet, the effects of 15 g/kg supplementary leucine were compared with isonitrogenous glycine supplements. Half of the diets were also marginally deficient in pyridoxine and resulted in slower growth, but no interactive effect with leucine. The leucine supplement depressed excretion of N1-methylnicotinamide only in the groups receiving supplementary tryptophan. It was also associated with a depression in the level of nicotinamide nucleotides in the rats' livers that was not eliminated by addition of either 25 mg/kg nicotinic acid or 1 g/kg L-tryptophan. The existence of pellagra in Hyderabad, India, has been hypothesized to result from excessive leucine in the diet rather than from a deficiency of niacin/tryptophan. Neither our results with rats nor those of others appear to provide support for this hypothesis.
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PMID:Leucine excess and niacin status in rats. 295 74

Gender-related differences in self-reported depression, in biological factors putatively related to depression and in the associations between severity of illness and biological factors were investigated. To this end the Zung Self-Rating Depression Scale (SDS), the ratio L-tryptophan/valine + leucine (L-TRP/CAA) and basal cortisol in serum at 8 a.m. were determined in 51 depressed inpatients undergoing a dexamethasone suppression test (DST). In the total study group no significant relationships were established between severity of illness and either of the biological markers. In women, SDS correlated significantly (P less than 0.01) negatively with the ratio L-TRP/CAA and positively with post-dexamethasone cortisol (P less than 0.01). In men these relationships tended to be inverted. The differences in the two sexes between these correlation coefficients were significant (P less than 0.01). These gender-related differences in the relationships between self-reported depression and the biological variables could be explained by differential psychoneuroendocrine and psychobiochemical responses. Future work on the severity of illnesses in terms of biological factors must take into account these differential responses between depressed males and females.
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PMID:Sex-related differences in the relationships between self-rated depression and biological markers. 297 81


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