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)

1. A comparative study has been made of the abilities of members of a homologous series of aliphatic alcohols to release prostaglandins from the rat isolated perfused lung. 2. Infusions of low concentrations (0.002 mmol--0.2 mmol) of methyl, ethyl, n-propyl, i-propyl, n-butyl and t-butyl alcohol for periods of up to 5 min was accompanied by the continuous output of prostaglandins into the venous effluent, as measured by biological assay. Maximal release occurred with methyl and ethyl alcohols, the releasing abilities of the rest being in the order of n-propyl> i-propyl> n-butyl> >t-butyl. Radiomimmunoassay revealed that both PGE2 and PGF2 alpha were released by ethyl alcohol with the former being in up to 10 times greater quantities than the latter. However, the amounts of these prostaglandins failed to account for the total release of active substances as measured by bioassay. 3. Examination of concentration-response relationship showed that as the concentration of methyl, ethyl and n-propyl alcohol was increased prostaglandin output also increased, but that after reaching a maximum further increase in alcohol concentration resulted in diminished release. In contrast, the lowest concentration of i-propyl, n-butyl and t-butyl alcohol utilized (0.002 mmol) caused highest prostaglandin output and release declined as the concentration was increased. Release by ethyl alcohol (0.02 mmol) was inhibited by t-butyl alcohol (0.2 mmol). 4. Thus aliphatic alcohols can not only release prostaglandins but also depress release. Both properties appear to be possessed by each member of the series, their relative prominence varying in each compound. Release is the predominant action of the low molecular weight, short chain compounds whereas depression of release is the most prominent property of those of higher molecular weight, particularly the secondary and tertiary alcohols. 5. It is suggested that release occurs in response to low alcohol concentrations altering the nature of the water-cell membrane interface, thus producing changes in membrane protein configuration and activation of phospholipase A. Inhibition of release is probably a consequence of non-specific depression of cell function.
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PMID:Prostaglandin release by aliphatic alcohols from the rat isolated lung. 741 71

Low-frequency synaptic stimulation evokes long-term depression of synaptic strength. One hypothesis is that modification of AMPA receptors by phospholipase A2 causes long-term depression. A previous study reported bromophenacylbromide, a completely nonselective phospholipase A2 inhibitor, blocked long-term depression at Schaffer collateral-CA1 synapses in hippocampus. In contrast, I show here that 3-(4-octadecyl)-benzoylacrylic acid (OBAA), a much more potent and selective inhibitor of low and high molecular weight phospholipase A2, does not block long-term depression at these same synapses, indicating that phospholipase A2 is not necessary for modifications causing long-term depression.
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PMID:Phospholipase A2 activation is not required for long-term synaptic depression. 773 25

In previous experiments, we have shown that antidepressants such as desipramine (DMI) can induce axonal regeneration of noradrenergic locus coeruleus neurons. In this article, we suggest that phospholipase A2 is involved in the molecular mechanism of the antidepressant-induced regeneration of brain noradrenergic axons. The effects of the PLA2 inhibitors, mepacrine (MEP) or 4-bromphenacyl bromide (BPB), upon the DMI-induced regeneration of noradrenergic axons in the rat cerebral cortex were assessed by either histofluorescence or immunohistochemistry using an antibody to dopamine-beta-hydroxylase. Symmetrical sites of the frontal cortex in both hemispheres were pretreated with 6-hydroxydopamine (6-OHDA). Then, the same cortical site of one hemisphere was infused with DMI by means of osmotic minipumps for more than 2 weeks, while the corresponding cortical site of the other hemisphere was infused with DMI plus MEP or BPB. It was found that the PLA2 inhibitors could attenuate the DMI-induced regeneration of noradrenergic axons. Thus, if axonal retraction or degeneration of brain noradrenergic neurons is involved in the pathogenesis of clinical depression, elucidating the malfunction of the PLA2 systems may provide substantial evidence to aid in our understanding of the cause of depression at the molecular level.
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PMID:Effects of phospholipase A2 inhibitors on the antidepressant-induced axonal regeneration of noradrenergic locus coeruleus neurons. 784 24

Low-frequency stimulation of the Schaffer-commissural pathways in slices prepared from juvenile rats (postnatal day 10-15) results in a long-term depression (LTD) of synaptic transmission. 30 min after 5 min of stimulation at 5 Hz, the response to the stimulated pathway was decreased by 36%, whereas the response to an unstimulated pathway projecting to the same neuronal population was decreased by 20%. Stimulation in the presence of the NMDA receptor antagonist AP5 completely prevented homosynaptic LTD. The phospholipase A2 inhibitor, bromophenacylbromide, also significantly reduced the extent of LTD in both the stimulated and control pathways. LTD was accompanied by a decrease in paired-pulse facilitation, suggesting a change in transmitter release. It also resulted in an increased effect of iontophoretically applied perchlorate, an ion which increases both the affinity of glutamate for the synaptic alpha-amino-3-hydroxy-5-methyl-4- isoxazole propionate (AMPA) receptors and synaptic responses, suggesting a change in postsynaptic receptors. These findings indicate that certain stimulation paradigms produce a combination of pre- and postsynaptic modifications that could underlie changes in synaptic efficacy.
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PMID:Blockade of long-term depression in neonatal hippocampal slices by a phospholipase A2 inhibitor. 791 48

The anti-inflammatory activity of avarol and avarone, sesquiterpenoid derivatives from the Mediterranean sponge Dysidea avara, was investigated. Both compounds potently inhibited paw oedema induced by carrageenan (approximated ED50 = 9.2 and 4.6 mg/kg, p.o., respectively) as well as ear oedema induced by 12-O-tetradecanoylphorbol acetate (TPA; ED50 = 97 and 397 micrograms/ear, respectively) in mice, with effects comparable to those of indomethacin. In A23187-stimulated rat peritoneal leukocytes, avarol showed an IC50 = 0.6 and 1.4 microM for inhibition of leukotriene B4 and thromboxane B2 release, respectively, with avarone showing a slightly lower potency. Both marine metabolites failed to show xanthine oxidase inhibitory activity or superoxide scavenging effects but were potent inhibitors of superoxide generation in rat peritoneal leukocytes activated by different stimuli, with an IC50 below the microM range. Only avarol was able to inhibit human recombinant synovial phospholipase A2 activity with an IC50 = 158 microM, and thus this compound showed a potency higher than that of mepacrine. Avarol and avarone effectively control acute inflammation in experimental models after either oral or topical administration and their anti-inflammatory activity may result from inhibition of eicosanoid release and depression of superoxide generation in leukocytes.
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PMID:Avarol and avarone, two new anti-inflammatory agents of marine origin. 801 50

Proteolytic enzymes, lipase, kinins, and other active peptides liberated from the inflamed pancreas convert inflammation of the pancreas, a single-organ disease of the retroperitoneum, to a multisystem disease. Adult respiratory distress syndrome, in addition to being secondary to microvascular thrombosis, may be the result of active phospholipase A (lecithinase), which digests lecithin, a major component of surfactant. Myocardial depression and shock are suspected to be secondary to vasoactive peptides and a myocardial depressant factor. Coagulation abnormalities may range from scattered intravascular thrombosis to severe disseminated intravascular coagulation. Acute renal failure has been explained on the basis of hypovolemia and hypotension. The renin-angiotensin alterations in acute pancreatitis (AP) as mediators of renal failure need to be studied. Metabolic complications include hypocalcemia, hyperlipemia, hyperglycemia, hypoglycemia, and diabetic ketoacidosis, of which hypocalcemia has been long recognized as an indicator of poor prognosis. The pathogenesis of hypocalcemia is multifactorial and includes calcium-soap formation, hormonal imbalances (e.g., parathyroid hormone, calcitonin, glucagon), binding of calcium by free fatty acid-albumin complexes, and intracellular translocation of calcium. Subcutaneous fat necrosis, arthritis, and Purtscher's retinopathy are rare. The various prognostic criteria of AP and other associated laboratory abnormalities are manifestations of systemic effects. Early recognition and appropriated management of these complications have resulted in improved prognosis of severe AP.
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PMID:Acute pancreatitis: a multisystem disease. 804 85

Stimulation of synaptoneurosome suspensions by the neurotransmitter glutamate gives rise to rapid loading of ribosomes onto mRNA and increased incorporation of amino acids into trichloroacetic acid-precipitable polypeptides. Metabotropic glutamate receptors (mGluRs) are responsible for this effect. Although simultaneous Ca2+ entry and mGluR stimulation do not change the response, entry of Ca2+ 30 s or 3 min before mGluR stimulation markedly depresses the polyribosomal loading. Either NMDA or ionophore (A23187) produces the depression. A calmodulin antagonist, W7, alleviates the effect, suggesting that inactivation of phospholipase A2 by calcium-calmodulin-dependent kinase II is partially responsible for the phenomenon. Thus, interaction between different classes of glutamate receptors affects the control of protein translation at the synapse. This effect may partially explain recent observations of negative interactions between receptor classes in induction of long-term potentiation.
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PMID:Calcium ion impedes translation initiation at the synapse. 852 53

The effects of the venom of the Sahara sand viper (Cerastes vipera) were studied on isolated chick biventer cervicis, isolated rat atria and vas deferens preparations, and on the electrocardiogram of anaesthetized rats. Effects on 3H-noradrenaline uptake were studied using rat brain synaptosomes. At 50 micrograms/ml and 100 micrograms/ml, the venom caused a transient increase in rate and force of contractions of the rat atria followed by an irreversible depression. These effects were not prevented by atenolol, atropine or a combination of the two. In the presence of 25 microM lignocaine, the effects of venom on rat atria were reversible by washing. At 100 micrograms/ml, the venom transiently increased responses of vas deferens preparations to indirect stimulation, but had little effect on responses to noradrenaline, KCl, and ATP. In the presence of an alpha 1-adrenoceptor antagonist (prazosin) or a P2-purinergic receptor antagonist (suramin), the venom still significantly increased twitch height and responses to noradrenaline but not to KCl or ATP. The effect of the venom did not change after exposure to a combination of prazosin, suramin and tetrodotoxin. The venom (100 micrograms/ml) significantly decreased twitches to indirect and direct stimulation in chick biventer cervicis preparations. Responses to exogenously applied acetylcholine, carbachol and KCl were also decreased. Venom blocked the synaptosomal uptake of 3H-noradrenaline (IC50 = 5 micrograms/ml), and caused severe bradycardia in vivo. Some of the direct effects on muscle preparations are possibly due to the venom's phospholipase A2 activity.
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PMID:Some pharmacological studies on the effects of Cerastes vipera (Sahara sand viper) snake venom. 859 81

Microglia and astrocytes are transformed into reactive glia (RG) by brain disease and normal function. Eicosanoids and nitric oxide (NO), two intercellular mediators, may influence gliosis. We investigated how drugs that alter production of these paracrine signals effect induction of glial reactivity from spreading depression. Unilateral (left) neocortical spreading depression was induced in 95 halothane anesthetized rats by intracortical injections of 0.5 M KCl, with or without drug treatment (five animals/group). Immunohistochemical staining (IS) intensity using the OX-42 and anti-glial fibrillary acidic protein (GFAP) antibodies determined reactivity in microglia and astrocytes, respectively. After 3 days, brains were processed for OX-42 and GFAP-IS and mean optical densities (OD) of IS were measured. Average OD's (for OX-42) and the log ratio (left/right) of OD's (OX-42 and GFAP) were compared to normal animals. Spreading depression induced significant log ratios for both OX-42- and GFAP-IS (P's < 0.01). However, dexamethasone (a glucocorticoid), nordihydroguaiaretic acid (a lipoxygenase inhibitor), and nitroprusside (a NO donor) prevented significant left sided and log ratio OD values for microglia (P's > 0.05). L-Name, a NO synthase inhibitor, caused significant increases in left and right OD's for microglia (P's < 0.05). Mepacrine, a phospholipase A2 inhibitor, Indomethacin, a cyclooxygenase inhibitor, and phenylephrine, an adrenergic agonist, did not prevent induction of significant OX-42 log ratios (P's < 0.01, 0.05, 0.01), and resulted in increases in left side OD's (P's < 0.01, 0.05, 0.05). Significant GFAP log ratios occurred after spreading depression in all drug groups, P's < 0.01. Thus, induction of reactivity in microglia is more sensitive to eicosanoids and NO than in astrocytes.
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PMID:Eicosanoids and nitric oxide influence induction of reactive gliosis from spreading depression in microglia but not astrocytes. 872 5

After a bout of intense exercise, especially in untrained persons recovery of muscle force is often slow. Force depression is much more marked at low frequencies of stimulation than at high frequencies ("low-frequency fatigue') and recovery can take more than 1 day. Delayed force recovery is also seen in single muscle fibres from frog and mouse after fatigue induced by repeated, brief contractions. Evidence from our own and other laboratories indicates that the impairment is unlikely to result from metabolic changes and points to a defect in excitation-contraction coupling. We demonstrate that the likely site of failure is in the coupling between t-tubule depolarization and release of Ca2+ from the SR. The causative agent appears to be a localized increase in cytoplasmic Ca2+ which initiates some disruptive process, which can, however, be fully reversed, albeit slowly. Our experimental evidence does not support the involvement of Ca(2+)-activated proteases. Attempts to clarify the possible role of Ca(2+)-activated lipases (phospholipase A2) and Ca2+/calmodulin have been hampered by side-effects of available inhibitors. Efforts to clarify how Ca2+ exerts its effects are continuing.
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PMID:Slow recovery of force in single skeletal muscle fibres. 872 79


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