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)

Twenty-four acutely ill schizophrenic patients (DSM-III-R), 18-42 years old, were treated for 6 weeks with sulpiride. Sulpiride was administered in three different daily dosages (400, 800 or 1200 mg) according to a double dummy blind randomized administration schedule. The psychopathology of the patients was rated by the Comprehensive Psychopathological Rating Scale (CPRS) and the Nurse's Observation Scale for Inpatient Evaluation (NOSIE). The monoamine metabolites homovanillic acid (HVA), 5-hydroxy-indoleacetic acid (5-HIAA), 4-hydroxy-3-methoxy-phenylglycol (HMPG) and the amino acids tyrosine, tryptophan, glutamate and glutamine were measured in serum before and once a week during sulpiride treatment. There were no significant correlations between the CPRS or the NOSIE morbidity scores and the biochemical measures before drug treatment. HVA levels were not correlated to rating scores during treatment, but after 6 weeks HVA had decreased significantly in the patients with a good response but not in the patients with a poor response. A negative relationship between 5-HIAA levels and depressive and negative symptoms was found. Non-responders according to the subscale for depression had low 5-HIAA levels throughout the treatment. An increase of tryptophan was correlated to improvement in the early part of treatment. High levels of glutamate or glutamine were found in non-responders before treatment. During treatment an increase of the glutamate level was correlated to improvement. Low levels of glutamine were related to improvement according to global and NOSIE (total) rating scores. Peripheral biochemical measures may be a valuable tool in the study of pathophysiological mechanisms and treatment effects in patients with schizophrenia.
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PMID:Relationships between clinical effects and monoamine metabolites and amino acids in sulpiride-treated schizophrenic patients. 236 52

It was demonstrated in experiments on male Wistar rats that preliminary use of a perfusion liquid containing the synthetic tripeptide Tyr-Pro-Arg facilitates restoration of the indices of the function of isolated perfused hearts (IPH) of rats after stress caused by 30-minute total ischemia (TI) of the myocardium at 37 degrees C. Irreversible damages to the myocardium and total depression of its function were recorded in the controls in this period of TI. The optimal concentration of the preparation in the perfusion fluid providing for restoration of IPH function by 80-100% of the initial level is 3.10(-9) M. The protective effect of the preparation is preserved in preliminary (30 minutes prior to TI) intraintestinal and intragastric administration of 10 micrograms/kg. Administration of Tyr-Pro-Arg separately or together with the beta-blocking agent propranolol as well as with atropine, which blocks the vagus effect, revealed their concurrent relations at the level of the adrenergic receptors. It is concluded that the cardioprotective effect of Tyr-Pro-Arg in TI stress is determined to a great measure by its inhibiting effect on the adrenergic mechanisms of cardiac activity regulation. Experiments in which the Ca2+ concentration in the perfusion fluid was increased threefold before and after TI showed that after using Tyr-Pro-Arg the IPH function after TI was restored and stimulated sharply by the increased Ca2+ concentration, in contrast to the controls in which stimulation of cardiac activity before TI increased the ischemic damage to the myocardium.
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PMID:[The cardioprotective effect of a new Soviet synthetic analog of the endogenous opioids in stress due to total myocardial ischemia and its mechanisms]. 238 41

Multiple administrations of high doses of methamphetamine to rats cause long-term depression of both dopamine and serotonin synthesis. Coadministration of the catecholamine synthesis inhibitor, alpha-methyl-p-tyrosine, antagonizes this effect of methamphetamine on both neurotransmitter systems. However, when catecholamine synthesis was maintained by the administration of L-dopa and the peripheral decarboxylase inhibitor R04-4602, alpha-methyl-p-tyrosine no longer prevented the effects of methamphetamine on either dopamine or serotonin synthesis. In addition, the administration of the specific dopamine uptake blocker, amfonelic acid, significantly attenuated the changes in the serotonin synthesizing enzyme, tryptophan hydroxylase, resulting from multiple high doses of methamphetamine. The ability of a single administration of methamphetamine to depress tryptophan hydroxylase was also dependent on catecholamine synthesis. These results suggest that dopamine plays an important role in the changes mediated by the administration of methamphetamine in both the dopaminergic and serotonergic systems.
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PMID:Role of dopamine in the neurotoxic effects of methamphetamine. 240 67

The relationship between the ratio in plasma of tryptophan to competing amino acids, which indicates brain serotonin synthesis, and the clinical response in depressed patients to treatments that act by enhancing brain serotoninergic function has been studied. There was a significantly positive correlation between the pretreatment plasma tryptophan ratio and the final depression score in patients treated with L-tryptophan or amitriptyline, and a trend towards a positive correlation in patients treated with lithium plus L-tryptophan or clomipramine. Patients with a low plasma tryptophan ratio generally showed greater clinical improvement than patients with a high ratio. When the plasma tryptophan ratio and the ratio in plasma of tyrosine to competing amino acids were considered together there was also a significant relationship between clinical and biochemical findings in patients treated with imipramine. These studies strongly indicate that brain serotoninergic function can be disturbed in depressed patients and, thus, lend support to the serotonin deficiency hypothesis in depression. Evidence has furthermore been presented which suggests that, rather than a low brain serotonin level per se, the hypofunction may be associated with disturbances in adaptive and regulatory mechanisms, e.g. postsynaptic serotonin receptors.
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PMID:Tryptophan to competing amino acids ratio in depressive disorder: relation to efficacy of antidepressive treatments. 241 37

Concentrations of several large neutral amino acids (LNAA) were earlier shown to be low, especially in brain, in rats fed a low protein diet containing a mixture of LNAA analogues. The purpose of this study was to learn if individual analogues would induce similar effects. Four hours after first feeding one meal containing norleucine, norvaline, alpha-aminophenylacetic acid, or alpha-aminooctanoic acid, concentrations of branched-chain amino acids were low in plasma, brain, liver and muscle; tyrosine and phenylalanine were more effectively reduced in brain than in other tissues. Lysine and arginine concentrations were low in brains of rats fed the basic amino acid analogue, homoarginine; concentrations of large and small neutral amino acids were unchanged. Dopamine was not low in brains having low tyrosine levels; serotonin was low in rats receiving alpha-aminooctanoate, the only analogue associated with a significant depression in brain tryptophan. The results suggest that the analogues have differing abilities to alter concentrations of tissue components. Decreases, especially in brain amino acid concentrations, may result from selective competition by analogues of a given transport class with natural amino acids transported from blood into brain by the same system.
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PMID:Tissue amino acids in rats fed norleucine, norvaline, homoarginine or other amino acid analogues. 242 57

1. Actions of the neuropeptide FMRFamide (Phe-Met-Arg-Phe-NH2) and its derivative YGG-FMRFamide (Tyr-Gly-Gly-Phe-Met-Arg-Phe-NH2) on Ca2+ current were examined in identified, voltage-clamped neurones in the abdominal ganglion of Aplysia californica. 2. 'Puffed' application of either peptide at concentrations of 1-50 microM was followed by a transient partial suppression of pharmacologically isolated inward Ca2+ current elicited by a depolarizing step. At 20 degrees C, suppression was maximal 10-25 s following the brief puff of peptide, and lasted up to 90 s. Bath application of peptide had a steady suppressing effect, showing little if any desensitization. 3. Alternative sources of inward current suppression were ruled out, indicating that application of FMRFamide or YGG-FMRFamide produces a true decrease in Ca2+ current, rather than enhancement of possible contaminating outward (K+, H+ or Cl-) currents. 4. FMRFamide and YGG-FMRFamide were equally effective in suppressing Ca2+ current (apparent dissociation constant, KD* approximately 10 microM). However, only 30-50% of the total Ca2+ current elicited by voltage steps to above +10 mV appeared to be susceptible to suppression by even saturating concentrations of peptide. This, as well as a reduced effect of the peptides on Ca2+ current which was observed at potentials below +10 mV, may perhaps result from the presence of more than one class of Ca2+ channels, only one of which is sensitive to FMRFamide. 5. FMRFamide eliminated a constant fraction of Ca2+ current at all potentials above +10 mV, and had no direct effect on activation or inactivation of the remaining current. This behaviour is consistent with reduction in the number of functional Ca2+ channels by the peptide. 6. Suppression of Ca2+ current produced a concomitant depression of Ca2+-dependent K+ current, which was shown previously to be insensitive to FMRFamide when activated by direct ionophoretic injection of Ca2+ into the cell. 7. The effect of FMRFamide on Ca2+ current was normal following interference with or activation of known second-messenger systems, those involving adenosine 3',5'-cyclic monophosphate (cyclic AMP), cyclic GMP, Ca2+, inositol trisphosphate and protein kinase C. 8. Suppression of Ca2+ current by FMRFamide appeared to be mediated by the same receptor as enhancement by the peptide of K+ current resembling IK(S) (K+ current suppressed by serotonin), an effect seen in most of the same cells. Both effects of FMRFamide were mimicked by injection of guanosine 5'-O-(3-thiotriphosphate) (GTP-gamma-S) into the cell, suggesting that the peptide may exert its effects by activating a guanosine 5'-triphosphate (GTP)-binding protein
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PMID:Suppression of calcium current by an endogenous neuropeptide in neurones of Aplysia californica. 244 95

1. The effects of a six week period of streptozotocin-induced diabetes on tissue catecholamines and on in vivo noradrenaline turnover were assessed in rats. 2. Noradrenaline concentrations measured in heart ventricle, terminal ileum, vas deferens, spleen and adrenal tissue from the diabetic rats were all found to be elevated compared to those found in control rat tissues. The adrenaline contents of the adrenal glands were also raised in these animals. 3. Noradrenaline turnover in heart ventricle, terminal ileum and vas deferens was estimated from the decline in tissue content of the amine following inhibition of its synthesis with alpha-methyl-p-tyrosine. Turnover was found to be increased in all three tissues. 4. The involvement of the polyol pathway in the above changes was investigated by examining the effects of continuous treatment with an aldose reductase inhibitor, Statil (ICI 128436) or dietary myo-inositol supplementation. Either treatment was found to prevent or reduce the increases in tissue noradrenaline and in its turnover. Myo-inositol treatment also partially prevented the rise in adrenal adrenaline. 5. It is concluded that the elevation of tissue catecholamines and of noradrenaline turnover by diabetes was related to myo-inositol depletion secondary to excessive sorbitol synthesis. Possible mechanisms for the observed increase in noradrenaline turnover could involve Na+, K+-ATPase depression.
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PMID:Tissue noradrenaline and the polyol pathway in experimentally diabetic rats. 250 23

Current theories of affective disorders do not account for many of the biological markers replicated in patient studies. We link many biological findings in a reasonable physiological relationship, compatible with mechanisms of action of pharmacological and electroshock therapies for depression. We propose that excessive phospholipase-A2 (PLA2) activity disrupts membrane fluidity, composition, and therefore, the activity, of membrane-dependent proteins. Similar disruptions in these proteins are documented in depressed patients and can be accounted for by excessive PLA2 activity. This paradigm accounts for disturbances in the activity of Na-K-ATPase, beta2- and alpha2-adrenergic receptors, MAO, norepinephrine and serotonin uptake, and imipramine binding. Disturbances in other membrane-dependent proteins, tyrosine and tryptophan hydroxylase, can explain the biogenic amine hypothesis. Inhibition of glucocorticoid receptor and TRH receptor binding to their respective ligands by PLA2 may explain patient nonsuppression in the Dexamethasone Suppression Test and poor response in the TRH stimulation test. Physiological regulators of PLA2 activity; calcium, cortisol, estrogen, progesterone, and PGE2 are documented abnormalities in some patients with affective disorders and consistent with excessive PLA2 activity. Thus, postpartum depression and premenstrual tension syndrome may be described in the paradigm. The mechanisms of action of tricyclic antidepressants, lithium, electroconvulsive shock, and some novel antimanic agents can be described in terms of alterations of PLA2 activity. Interestingly, ethanol perturbs membrane fluidity and membrane-bound enzymes in a manner similar to excessive PLA2 activity. A hereditary factor predisposing patients to affective disorders may be a gene defect at either PLA2 or in its regulation.
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PMID:Are disturbances in lipid-protein interactions by phospholipase-A2 a predisposing factor in affective illness? 256 35

Neurons with co-localized cholecystokinin (CCK) and dopamine (DA) are present predominantly in the ventral tegmental area (VTA) and project mainly to the caudal part of the medial nucleus accumbens. The activity of this dopaminergic system can be evaluated by means of the intracranial self-stimulation behaviour (ICSS) on male Wistar rats having chronic electrodes implanted into the medial forebrain bundle in the postero-lateral area of the hypothalamus. The direct injection of the CCK analogue BOC(Nle28;Nle31)CCK27-33 (BDNL-CCK7) into a lateral ventricle decreased the electrical self-stimulation of the medial forebrain bundle. Nevertheless, this decrease in self-stimulation was steeper (immediately after the injection vs a delay of +/- 5-10 min.) than the CCK8-induced ICSS depletion. The intracerebroventricular (ICV) injection of 150 pmol and 1000 pmol BC-197 (BOC-D.Asp-Tyr(SO3H)-Nle-D.Lys-Trp-Nle-Asp-Phe-NH2) was ineffective to modify the self-stimulation behaviour when administered alone while a 150 pmol BC-197 dosage was able to antagonize the decreasing effect of 150 pmol CCK-8 on ICSS. Nevertheless, a dosage 6 times as important, i.e. 1000 pmol BC-197, was needed to antagonize the depression induced by 150 pmol BDNL-CCK7 on ICSS behaviour. These results support the equipotence of BDNL-CCK7 to CCK-8 in decreasing the self-stimulation behaviour after their direct administration into the lateral ventricle. They further give evidence of the relevance of BC-197 in antagonizing the respective effects of both compounds on the ICSS.
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PMID:Similar potencies of CCK-8 and its analogue BOC(Nle28;Nle31)CCK27-33 on the self-stimulation behaviour both are antagonized by a newly synthesized cyclic CCK analogue. 273 84

The potassium stimulated release of [3H]norepinephrine ([3H]NE) from terminal fields of locus coeruleus projections can be inhibited in a dose-dependent manner by mu and kappa selective opioids. Chronic exposure to morphine for six days decreases the maximum achievable depression by the mu selective agonist Tyr-D-Ala2-Gly-Me(Phe)-Gly-ol (DAGO), but has no effect on the degree of inhibition produced by the kappa selective opioid U50,488H.
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PMID:Effects of prior exposure to morphine on the opioid inhibition of the stimulated release of [3H]norepinephrine from guinea pig cortex slices. 282 6


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