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)

The cyclic adenosine monophosphate (cAMP) responses to prostaglandin E1 (PGE1) in platelets and leukocytes from drug-free schizophrenic patients, depressive patients, and normal controls have been compared. Both schizophrenic and depressive patients had a significantly lower platelet cAMP response to PGE1 than controls. The platelet cAMP response to PGE1 did not discriminate among exacerbated, remitted, and poor-prognosis schizophrenic patients, or between exacerbated and remitted depressive patients. The cAMP response to PGE1 was negatively correlated with global symptom severity in actively ill schizophrenic patients, but was not correlated with symptom severity in exacerbated depressive patients. The leukocyte cAMP response to PGE1 did not differ among normal controls, schizophrenic patients, and depressive patients. These data indicate that a diminished platelet cAMP response to PGE1 may be a marker common to both schizophrenia and depression but that this effect does not extend to a cAMP-linked PGE1 receptor on another blood cell type.
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PMID:Prostaglandin receptor sensitivity in psychiatric disorders. 301 69

1 We compared the effects of endotoxin on pulmonary prostaglandin E1 (PGE1) removal in groups of rabbits pretreated with the cyclo-oxygenase inhibitor, indomethacin, or nafazatrom (Bay g 6575), which has been shown to increase plasma prostacyclin concentrations. 2 In untreated animals, endotoxin transiently decreased pulmonary removal of [3H]-PGE1, caused pulmonary hypertension, systemic hypotension and increased plasma concentrations of PGE2 and 6-keto-PGF1 alpha. 3 Indomethacin pretreatment prevented the transient decrease in pulmonary removal of [3H]-PGE1 in response to endotoxin, prevented the haemodynamic effects and inhibited prostaglandin synthesis. Pretreatment with nafazatrom did not affect the decreased pulmonary removal of [3H]-PGE1, exacerbated the haemodynamic response, reduced survival and potentiated the increase in circulating 6-keto-PGF1 alpha. 4 We conclude that indomethacin acts to prevent the depression of pulmonary [3H]-PGE1 removal by eliminating surface area changes associated with endotoxin-induced pulmonary vasoconstriction. 5 These data suggest that nafazatrom treatment results in exacerbation of the endotoxin-induced systemic hypotension presumably due to its effect on increased plasma prostacyclin during the later phase of endotoxaemia.
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PMID:Effect of nafazatrom and indomethacin on pulmonary removal of prostaglandin E1 after endotoxin in rabbits. 331 Dec 63

In the liver of adjuvant arthritic rats perfused with a hemoglobin-free buffer solution, the rate of metabolism of a model drug, 2,6-dichloro-4-nitroanisole, was approximately half that of the control, while the bile flow rate was normal. Granulation tissue extracts and arthritic rat serum had no effect on the activity of CNA metabolism in normal rat liver preparations. In the perfused normal rat liver, the rate of CNA metabolism was inhibited by addition of prostaglandin (PG) E1, PGE2, and PGF2 alpha, respectively, in a final concentration of 0.5 microM. The inhibition by PGE1 was increased in the concentration range from 0.1 to 2.5 microM. The bile flow rate was not affected by the added PGs. However, these PGs had no direct effect on the CNA demethylating activity of the isolated hepatocytes from normal rat liver in a high concentration of 10 microM. Serotonin stimulated slightly CNA metabolism and bile production in the perfused livers by the intermittent infusion, but was without effect in the isolated hepatocytes. Epinephrine and histamine had no significant effect on CNA metabolism in both liver preparations. A similar pattern of the inhibition of CNA metabolism by PGs was reproduced in the normal rat liver perfused with the medium containing the supernatant of the hepatic nonparenchymal cells incubated in the presence of PGE1. The involvement of liver sinusoidal cells as secretory cells in depression of hepatic drug metabolism has been discussed.
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PMID:Prostaglandins: a possible mediator to inhibit hepatic drug metabolism in adjuvant arthritic rats. 346 29

The protective effect of prostaglandins (PGs) against cerebral hypoxia/anoxia was investigated with a variety of experimental models in relation to their CNS depressant effects in mice. Furthermore, the effect of PGs on the changes of cerebral energy metabolites and cyclic nucleotide was examined in hypoxic mice. Mice were given s.c. doses of PGs 30 min before tests. Among the PGs tested, treatment with PGD2, PGE1 and PGI2 Na showed a consistent and dose-dependent protection against cerebral anoxia induced by all models studied: histotoxic anoxia by KCN, hypobaric hypoxia, normobaric hypoxia and decapitation-induced gasping. However, PGA1, PGA2, PGB1, PGB2, PGE2, PGF1 alpha, PGF2 alpha and 6-keto-PGF1 alpha at a dose of 3 mg/kg were without effect against normobaric hypoxia and gasping duration. The three PGs, i.e. PGD2, PGE1 and PGI2 which showed anti-hypoxic effects decreased locomotor activity and potentiated hexobarbital-induced sleep. On the other hand, PGE2, PGA1, PGA2 and PGB2 also caused a decrease in locomotor activity. Similarly, PGE2 and PGA1 caused a potentiation of hexobarbital-induced sleep, but interestingly they did not cause clear-cut increase in cerebral resistance to hypoxia, in contrast with the former three PGs. Thus general depression of CNS function appears not to be responsible for the PGD2-, PGE1- and PGI2-induced increase in cerebral resistance to hypoxia. The levels of Cr-P and ATP were significantly reduced and those of ADP and AMP were markedly elevated in hypoxic brain, resulting in a decrease in a calculated energy charge potential. The lactate level and lactate/pyruvate ratio increased and the glucose level decreased markedly.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Protective effect of prostaglandins D2, E1 and I2 against cerebral hypoxia/anoxia in mice. 354 99

We previously demonstrated the suppression of cell-mediated immunity to Listeria monocytogenes by Pseudomonas aeruginosa-induced, macrophage-like cells. The present study was undertaken to evaluate the mechanism for this suppression. P. aeruginosa supernatant was shown to activate macrophages by the criteria of increased bactericidal capacities and increased attachment to glass surfaces. Acquired cellular resistance to L. monocytogenes could also be inhibited by macrophages from L. monocytogenes-pretreated mice. The depression of acquired immunity by P. aeruginosa- or L. monocytogenes-activated macrophages did not appear to be due to a reduction of antigenic stimulus after nonspecific macrophage activation. In contrast, our findings suggest that suppression is mediated by activated macrophages through a prostaglandin-dependent mechanism. In vivo administration of aspirin blocked the immunosuppressive effect of P. aeruginosa- or L. monocytogenes-activated cells. Moreover, the suppressive activity of supernatants of macrophages from Listeria-infected mice was reversed when indomethacin was present during supernatant generation. Finally, prostaglandin E1 treatment in vivo profoundly inhibited the induction of cell-mediated immunity to L. monocytogenes. The possible role and mechanism of prostaglandin in suppressing cellular immunity to intracellular bacteria are discussed.
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PMID:Suppression of cellular immunity to Listeria monocytogenes by activated macrophages: mediation by prostaglandins. 392 50

The effects of cyclosporin A, prostaglandin E1 and indomethacin were studied on lectin-dependent cell-mediated cytotoxicity (LDCC) against adherent HEp-2 human epipharynx carcinoma target cells. LDCC activity by human peripheral blood lymphocytes was evaluated by detachment from the monolayer of [3H]thymidine-prelabelled HEp-2 cells in a 24-h assay at 50:1 effector:target cell ratio in the presence of 25 micrograms/ml concanavalin A. Under these conditions, but without concanavalin A, considerable natural cell-mediated cytotoxicity was not elicited although LDCC was significantly augmented in the presence of concanavalin A. Addition of both cyclosporin A (0.1, 1.0 or 10 micrograms/ml) and prostaglandin E1 (10(-8), 10(-7) or 10(-6) M) dose-dependently suppressed LDCC activity. Indomethacin (0.1, 1.0 or 10 micrograms/ml) did not in itself influence LDCC although suppression of LDCC by cyclosporin A, but not prostaglandin E1, was abrogated in the presence of indomethacin. Similar to indomethacin, acetyl salicylic acid also reversed the inhibition of LDCC by cyclosporin A. In parallel experiments, cyclosporin A elicited a more than two-fold increase of prostaglandin E production under LDCC assay conditions as measured by radioimmunoassay. Contrary to LDCC, depression of concanavalin A induced blastogenesis by cyclosporin A was not influenced by indomethacin, suggesting that the inhibition by cyclosporin A of LDCC and concanavalin A-induced blastogenesis proceed via different mechanisms.
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PMID:Indomethacin abrogates the suppression by cyclosporin A of lectin-dependent cell-mediated cytotoxicity to HEp-2 cells. 395 49

Due to asymmetry of brain neurotransmitters and differential hemispheric information processing modes, it is suggested that the excessive use of one information processing mode could engender a state of brain reactivity whose neurochemical correlates would be either a rise in melatonin or beta-endorphin in systemic circulation. Since melatonin and beta-endorphin have opposite effects on lung-mediated regulation of prostaglandins, it is further suggested that the pulmonary inactivation of prostaglandin E1 would either be increased or inhibited. Low levels of PGE1 would engender high levels of PGE2 whose effects would explain the findings in schizophrenics of: 'reducing' pattern of visual evoked response, cerebral atrophy, and viral and autoimmune phenomena. The primacy of the disordered cognitive style in leading up to the immunological, biochemical and neuropathological processes is stressed. Implications of this model for understanding depression, anxiety and phobic disorders, autism, attention deficit disorder, obesity, alcoholism, smoking, drug addiction, sexual deviations, and certain psychosomatic and psychophysiological disorders are suggested.
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PMID:How information processing mode could affect prostaglandin E1 metabolism and lung inactivation: relevance of hemispheric specialization, neurotransmitter asymmetry and brain reactivity. 614 17

Compared to normal and other neurological disease (OND) controls, multiple sclerosis (MS) pre nylon wool (pre NW) and nylon wool passed (NWP)-peripheral blood cells' natural killer (NK) activity was more sensitive to prostaglandin E (PGE1); it was suppressed to a greater degree and at lower concentrations of PGE1. At the single cell level this was reflected by lower numbers of target-binding cells (TBCs) and fewer killers among the TBCs. ONDs and normal controls were equally sensitive to PGE1. Though PGE-producing cells were depleted in the NWP population of normal and control ONDs, MS patients still had indomethacin-sensitive NK suppressors in the NWP population; these apparently did not suppress at the single cell effector level but at the level of recycling. MS and OND cerebrospinal fluid (CSF) cells' NK activity could not be 'enhanced' by indomethacin. Depression of interferon (IFN)-induced NK by PGE1 was greater in MS than in OND or normal controls perhaps through its effect on IFN-induced recycling. All subjects' cells maintained sensitivity to PGE1 after overnight incubation in the presence of PGE-producing cells (pre NW) or exogenous PGE1. In sharp contrast to normal and OND controls, MS NWP cells were still inhibited by PGE1 even after overnight incubation in the absence of PGE1.
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PMID:Regulation of natural killer cell cytotoxicity by prostaglandin E in the peripheral blood and cerebrospinal fluid of patients with multiple sclerosis and other neurological diseases. Part 2. Effect of exogenous PGE1 on spontaneous and interferon-induced natural killer. 618 56

Alcohol has at least two actions on essential fatty acid (EFA) and Prostaglandin (PG) metabolism. It enhances the conversion of dihomogammalinolenic acid (DGLA) to PGE1 but it blocks the activity of the delta-6-desaturase, an enzyme necessary for replenishment of DGLA stores from dietary precursors. The acute effect of ethanol is therefore an increased production of PGE1 but chronic consumption will lead to depletion of DGLA and PGE1. Withdrawal from alcohol will lead to a precipitous fall in PGE1. PGE1 is known to have profound effects on the nervous system and behaviour. Patients with mania produce more PGE1 than normal while those with depression make less. Alcoholics may drink to maintain a normal PGE1 level, something which will require more and more ethanol as DGLA is depleted. In both animals and humans PGE1 or its precursor, gamma-linolenic acid (GLA) have been shown to attenuate the acute withdrawal syndrome. PGE1 injections prevent the development of fatty liver in alcohol-treated animals. Defective EFA and PGE1 metabolism are known to lead to increased fibrosis, reproductive failure, cardiomyopathy, cardiovascular disorders, gastritis and pancreatitis and could therefore be the basis for these disorders in alcoholics. A PGE1 deficiency could also be responsible for the fetal alcohol syndrome. Three other agents are known to produce constellations of fetal defects very similar to those found in the alcohol syndrome. These other factors are dihphenylhydantoin, lithium, and a deficiency of zinc. These three factors and excessive alcohol consumption all lead to PGE1 deficiency by different routes. If this concept is correct, the key to the management of alcoholism and its medical complications lies in the provision of GLA or DGLA, fatty acids which by-pass the alcohol blocked step and which are unfortunately unlikely to be present in any normal diet. Unlike many concepts of alcoholism and alcohol damage, the EFA/PGE1 idea is very readily testable and already has considerable experimental support.
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PMID:A biochemical basis for alcoholism and alcohol-induced damage including the fetal alcohol syndrome and cirrhosis: interference with essential fatty acid and prostaglandin metabolism. 625 73

Normal levels of lymphocyte cyclic AMP were found in fourteen of fifteen patients with primary hypogammaglobulinaemia. One patient with adult-onset hypogammaglobulinaemia had low cyclic AMP levels with a very poor rise after prostaglandin E1 stimulation. Five of the patients had severely depressed thymidine uptake by their phytohaemagglutinin-stimulated lymphocytes but there was no significant difference between their lymphocyte cyclic AMP levels and those of patients with normal lymphocyte responses. Removal of monocytes from concanavalin A-stimulated lymphocyte cultures from three of these patients did not affect the severe depression of leucine uptake. These findings indicate that the depression of lymphocyte response to mitogens seen in some patients with late-onset primary hypogammaglobulinaemia is not due to raised levels of lymphocyte cyclic AMP; and not usually due to prostaglandins released by monocytes in the cultures.
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PMID:Lymphocyte cyclic AMP levels in primary hypogammaglobulinaemia: lack of correlation with response to phytohaemagglutinin. 625 5


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