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)

After the demonstration that hypothalamic peptides can have a direct effect on the central nervous system, a series of studies was initiated to investigate the hypothesis that hypothalamic peptides could have an effect on emotions and affect. TRH was administered to 6 patients with endogenous depressions in a double-blind, cross-over design with transient improvements in the mental depression of 4 of the 6 patients. In a second study involving 8 seriously depressed patients given 1000 mug of TRH for 10 days, no significant antidepressant effect of TRH was observed. In a pilot, double-blind study of 18 women with endogenous depressions, the group receiving MIF-1 60 mg per day in a single daily dose for 6 days responded better than the placebo group, which in turn responded better than the group receiving MIF-1 150 mg per day. In a second, double-blind study testing MIF-1 in endogenous depressions, 5 patients met the criteria for substantial improvement out of a total of 8 receiving MIF-1 75 mg per day. In contrast, only one patient met these criteria in each of the remaining 2 groups, consisting of 10 patients receiving MIF-1 750 mg per day and 5 patients receiving placebo. Finally, 6 men complaining of decreased libido and/or potency were given intravenous injections of LHRH 700 mug or saline once daily for 3 consecutive days per week in a double-blind, cross-over design. In addition, 3 men were given much higher doses of LHRH in a single-blinded study. No substantial effect on libido or sexual performance was observed.
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PMID:Clinical investigations for emotional effects of neuropeptide hormones. 1 18

The effect of the factor that inhibits the release of melanocyte stimulating hormone (MSH), i.e., L-prolyl-L-leucyl-glycinamide (MIF), and L-prolyl-N-methyl-D-leucyl-glycinamide, an analog, on brain norepinephrine (NE), dopamine (DA) and serotonin (5-HT) turnover was examined in rats. The analog (40 mg/kg i.p.), in a fashion similar to MIF (40 and 5 mg/kg i.p.), increased brain DA turnover; only MIF (40 mg/kg i.p.) increased endogenous DA levels. The analog (40 and 5 mg/kg i.p.) decreased brain NE turnover; MIF at the same doses was ineffective. Neither MIF nor the analog affected rat brain 5-HT turnover or the 5-HTP-induced behavioural syndrome in the mouse. These results indicate that the analog, like MIF, exerts effects on central catecholamine turnover. The different biochemical profile of the analog compared to MIF may be importance with regard to potential clinical use in the treatment of Parkinson's disease and depression.
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PMID:Synthetic melanocyte stimulating hormone release-inhibiting factor (MIF). Part III: effect of L-prolyl-N-methyl-D-leucyl-glycinamide and MIF on biogenic amine turnover. 2 96

Fourteen di- and tripeptide analogues of MIF, Pro-Leu-Gly-NH2, have been synthesized and assayed for inhibition of oxotremorine-induced tremor. Replacement of Pro by HCO-Pro or cyclopentanecarboxylic acid gave inactive analogues, while some peptides of the general structure less than Glu-Leu-Gly-NR1R2 were highly active. Thus, R1 = C3H8 and R2 = H gave 4 times the activity of MIF, R1 = I-C3H8 and R2 = H gave 13 times the activity of MIF, and R1 = R2 = CH3 gave 29 times the activity of MIF. cyclo(-Pro-Leu-), Pro-Lys-Gly-NH2, and Pro-Arg-Gly-NH2 had no activity. Apparently, small modifications in the structure of MIF can yield highly active analogues with potential clinical value, e.g., in the treatment of Parkinson's disease or mental depression.
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PMID:Tripeptide analogues of melanocyte-stimulating hormone release-inhibiting hormone (Pro-Leu-Gly-NH2) as inhibitors of oxotremorine-induced tremor. 4 28

Humoral and cell-mediated immunity were studied in a group of patients with Wilson's disease not previously treated with D-penicillamine, and in a group of patients treated with the drug for more than two years. The previously untreated patients showed an exaggerated humoral immune response, i. e. increased levels of IgG and, IgM, higher titer of antibodies to Kunin's antigen, and depression of cell-mediated immunity, namely a decreased response to DNCB, decreased lymphocyte transformation after stimulation with Con A, PPD, Candida and streptokinase and a reduced response to streptokinase in the MIF test. After treatment the humoral response returned to normal, and in the case of IgA and antibodies to S. typhi O antigen, it even dropped below normal values. The cell-mediated immune response returned to normal with the exception of lymphocyte transformation by PHA and Candida albicans. In in vitro studies it was found that D-penicillamine had no influence on lymphocyte transformation when PHA and Con A were used as mitogens. With PPD as antigen, lymphocyte stimulation and migration inhibition were inhibited by concentrations of penicillamine ranging from 6 to 1000 microgram/ml.
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PMID:The influence of prolonged treatment with D-penicillamine on the immune response in Wilson's disease. 59 Mar 12

The effects of tripeptide melanostatine (Melano-Inhibitory Factor--MIF-1) in concentrations 10(-7)-10(-5) M on parameters of focal potentials (FPs) were studied in slices of rat olfactory and parietal cortex. The addition of MIF-1 to perfusion fluid caused in olfactory cortex the primary depression of FP amplitudes evoked by stimulation of the lateral olfactory tract (LOT); this depression was replaced by restoration and prolonged (30-40 min) enhancement of FP amplitudes and by appearance of additional FP components, such as disynaptic EPSPs and IPSPs. In parietal cortex slices MIF-1 caused the elevation of FP amplitudes evoked by stimulating adjoining points. The repetitive perfusion of slices with MIF-1 potentiated the peptide effect on the increase of FP amplitudes. During excitatory period MIF-1 influenced specifically the functional plasticity in olfactory cortex, having facilitated the induction and sustaining of post-tetanic potentiation (PTP). Data observed support the idea of the activatory influence of MIF-1 on the CNS at the cellular level, which is likely to lie in the ground of antidepressant properties of this peptide.
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PMID:Effects of melanostatine (MIF-1) on focal potentials in slices of rat brain cortex. 168 94

MIF-1 was tested in an animal model of depression that used unpredictable chronic stress. In this paradigm, rats received either no stressors or a daily protocol of a variety of stressors for 20 days, during which time daily, intraperitoneal injections of various compounds were given. The tricyclic antidepressant imipramine (5 mg/kg) and low doses (0.1 and 1.0 mg/kg) of MIF-1 significantly increased activity and decreased defecation in an open field on day 21. No dose of naloxone (0.01-10.0 mg/kg) acted as an antidepressant. A high dose (10.0 mg/kg) of MIF-1 significantly increased the effects of chronic stress and produced hyperalgesia. Chronically-stressed rats were significantly more analgesic than controls. The results indicate that MIF-1 can act as an antidepressant in this model.
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PMID:MIF-1 is active in a chronic stress animal model of depression. 256 1

Previous studies have shown effects of MIF-1 (prolyl-leucyl-glycinamide) and Tyr-MIF-1 (tyrosyl-prolyl-leucyl-glycinamide) in animal models of depression and also effects on dopaminergic function. These observations prompted us to examine whether the effects of the two peptides in the behavioral 'despair' test were modulated by dopamine antagonists. MIF-1 and Tyr-MIF-1, at the small dose of 0.01 mg/kg i.p. (24, 5 and 1 h before the test), produced a significant anti-immobility effect. This effect was antagonized by a single injection of either haloperidol or sulpiride, two dopamine receptor blockers. The same low dose of the tricyclic antidepressant desipramine was without significant effect in this test. The results indicate that Tyr-MIF-1, like MIF-1, is active in the behavioral despair test for antidepressants and that at least some of the CNS actions of these peptides are mediated by dopamine receptors.
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PMID:Blockade of brain dopamine receptors antagonizes the anti-immobility effect of MIF-1 and Tyr-MIF-1 in rats. 290 71

It was found that pregnant mice exhibit increased susceptibility to lethal action of Listeria monocytogenes, although there was no correlation between increase of susceptibility of animals to lethal effect of bacteria and weakening of elimination of microorganisms from the spleen. Increased susceptibility of animals to listeriosis was accompanied by weakening of some parameters of cellular immunity. In pregnant mice of strains C57Bl/6, naturally resistant to infections, inhibition of II-1 by macrophages was found which at the same time exhibited depression of chemotaxis. Weakening of these macrophage functions did not influence the development of delayed hypersensitivity to Listeria antigen (LA) in C57Bl/6 mice--the reaction which was suppressed in pregnant mice of A/J strain which is characterized by natural susceptibility to listeriosis. Inhibition of development of delayed hypersensitivity to LA in A/J pregnant mice was caused by defective function of dendritic cells and T lymphocytes. Dendritic cells of A/J pregnant mice exhibited limited ability of presentation of LA to immune T lymphocytes isolated from animals infected with L. monocytogenes or L. innocula. On the other hand, immune T cells of A/J mice cultured with LA exhibited inhibition of proliferation and production of MIF.
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PMID:[Weakness of cellular response to Listeria antigens in pregnant mice]. 823 43

Hostility is a risk factor for adverse health outcomes as diverse as cardiovascular disease and post-traumatic stress disorder (PTSD). Cytokines have been suggested to mediate this relationship. We investigated whether in healthy men a relation existed between hostility and T-cell mitogen-induced cytokines and chemokines. Male Dutch military personnel (n=304) were included before deployment. Eleven cytokines and chemokines were measured in supernatants of T-cell mitogen-stimulated whole blood cultures by multiplex immunoassay. Factor analysis was used to identify clusters of cytokines and chemokines. In a regression analysis hostility was related to the cytokine/chemokine clusters, and the potential risk factors age, BMI, smoking, drinking, previous deployment, early life trauma and depression. Explorative factor analysis showed four functional clusters; a pro-inflammatory factor (IL-2, TNFalpha, IFNgamma), an anti-inflammatory factor (IL-4, IL-5, IL-10), IL-6/chemokine factor (IL-6, MCP-1, RANTES, IP-10), and MIF. Hostility was significantly related to decreased IL-6/chemokine secretion and increased pro- and anti-inflammatory cytokines. There was an inverse relation between age and hostility scores. Early life trauma and depression were positively and independently related to hostility as well. This study represents a novel way of investigating the relation between cytokines and psychological characteristics. Cytokines/chemokines clustered into functional factors, which were related to hostility in healthy males. Moreover this relation appeared to be independent of reported depression and early trauma.
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PMID:Hostility is related to clusters of T-cell cytokines and chemokines in healthy men. 1864 Jul 86

MIF-1 (Pro-Leu-Gly-NH(2)) has potent therapeutic effects in depression and Parkinson's disease, but its CNS sites of production are not yet clear. In this study, the concentration of MIF-1 in different brain regions was measured by the multiple reaction monitoring technique on a 4000 QTRAP mass spectrometer. The limit of quantification was 300 fg of MIF-1, and limit of detection was 60 fg. The low molecular weight fractions of tissue homogenates from different regions of mouse brain were analyzed. The concentration of MIF-1 ranged from 22+/-3 fg/microg protein in cerebral cortex to 930+/-60 fg/microg protein in the hypothalamus. Moderate concentrations were also detected in all other regions tested, including the striatum, thalamus, and hippocampus. By incubation of stable isotope-labeled oxytocin with tissue preparations, it was also confirmed that oxytocin at least partially contributed to the production of MIF-1 in the hypothalamus by action of peptidases. Regional differences were also found. The results are the first to show the ultrasensitive quantification of MIF-1 in different brain regions, and support the neuromodulatory actions of MIF-1 in the striatum.
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PMID:Mass spectrometric quantification of MIF-1 in mouse brain by multiple reaction monitoring. 1954 Apr 26


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