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)

Single-unit extracellular recording was carried out in rats to characterize the effects of dynorphin and several structurally related peptides on hippocampal pyramidal cell activity. Dynorphin, applied electrophoretically or by pneumatic pressure, produced a dose-dependent depression of both spontaneous and glutamate-evoked discharge in a majority (63%) of CA1 and CA3 cells tested. In addition, a small number of cells in both cellular fields responded to the peptide with a prolonged elevation in firing. The inhibitory effects of dynorphin were not blocked by naloxone. Moreover, administration of des-tyrosine-dynorphin depressed the firing of pyramidal cells in a manner similar to that of the parent compound. Ethylketocyclazocine produced a mixed pattern of excitatory and inhibitory effects, whereas naloxone-sensitive elevations in firing were most often observed with the application of dynorphin-(1-8). Application of [Leu5]enkephalin produced only facilitations in pyramidal cell firing. The possibility is raised that biologically significant non-opiate actions, in addition to potent opiate-mediated effects, may occur upon release of pro-dynorphin peptides in the hippocampus.
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PMID:Electrophysiological effects of dynorphin peptides on hippocampal pyramidal cells in rat. 285 95

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

The vascular activity of arginine vasopressin (AVP) and selective AVP receptor antagonists was investigated in isolated arterial ring segments from human superior mesenteric arteries. AVP elicited a potent and concentration-dependent contraction in human mesenteric arterial rings with an EC50 value of 2.01 X 10(-9) M. The presence or absence of the vascular endothelium did not affect significantly AVP-induced contraction. AVP induced slight, although significant, tachyphylaxis in human mesenteric arteries. The selective vascular (V1) receptor antagonist [d(CH2)5 1Tyr(Me)2]AVP (SK&F 100273) shifted the concentration-response curves for AVP-induced vascular contraction to the right in a parallel manner (KB = 2.23 X 10(-9) M). A mixed V1/V2 receptor antagonist, [d(CH2)5 1D-Tyr(Et)2Val4desGly9]AVP (SK&F 101926), was also a potent antagonist of AVP-mediated vascular contraction; however, inhibition was marked by a nonparallel shift of the concentration-response curves with depression of maximum contraction. Furthermore, a relatively renal (V2) selective receptor antagonist [d(CH2)5 1D-Ile2Val4]AVP (SK&F 101485) was approximately 100-fold less potent at inhibiting AVP-induced vascular contraction (KB = 1.37 X 10(-7) M). These studies illustrate for the first time the in vitro effects of selective vasopressin receptor antagonists in isolated human blood vessels. Studies of other blood vessels and the design of therapeutically useful antagonists should proceed with the hypothesis that the vasopressin receptors mediating vascular contraction in human mesenteric arteries are of the V1 subtype.
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PMID:Human vascular vasopressin receptors: analysis with selective vasopressin receptor antagonists. 294 8

It has been suggested that post-burn myocardial depression may be due to coronary constriction which results in myocardial ischaemia. It has been demonstrated that the levels of vasopressin, a potent natural constrictor of blood vessels, increase four- to six-fold immediately after thermal trauma. Therefore, this substance could be responsible for post-burn coronary constriction and myocardial depression. This was tested using the dog anaesthetized with sodium pentobarbital receiving a 15 per cent total body surface area full thickness flame burn as the experimental model. Cardiac output was measured by the thermal dilution technique. Arterial blood pressure was sensed by a Stathem P-23 transducer. Cardiac force of contraction was measured by a Walton-Brody strain gauge arch sewn on the left ventricle. The results of this study showed a significant decrease in cardiac output, increase in peripheral resistance and decrease in myocardial force of contraction immediately after thermal trauma in untreated animals. The decrease in cardiac output and increase in peripheral resistance remained for the duration of the experimental observations (3 h). The decrease in force of contraction returned to pre-burn levels 1 h post-burn. Pretreatment of the experimental animals with d(CH2)5 Tyr(Me)AVP (SK&F 100273), a vasopressin V-1 receptor blocking agent, prevented the initial decrease in cardiac output, increase in peripheral resistance and decrease in the force of contraction. A correlation plot of peripheral resistance vs. cardiac force of contraction showed a positive correlation between these two variables in the pretreated animals.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of blockade of vasopressin V-1 receptors on post-burn myocardial depression. 296 92

The influence of drugs which modify the concentration of brain monoamines on the size of the 50% antitussive dose (AtD50) of morphine (M), dihydrocodeine (DC) and dextromethorphan (DX) was investigated in male Sprague-Dawley rats. The puncture electrode-induced cough method was used for inducing cough. The AtD50 was calculated by the "up and down" method. All drugs were injected i.p. Concentrations of norepinephrine (NE), dopamine (DA) and serotonin (5-HT) in the whole brain were measured by means of high performance liquid chromatography with electro-chemical detection. The values for the AtD50 of M, DC and DX were 1.22, 1.44, and 6.06 mg/kg, respectively. Reserpine (2.5 mg/kg/day, 2 days) produced depression of more than 80% in levels of NE, DA and 5-HT in the brain. This treatment resulted in a substantial reduction in the antitussive effect of the cough suppressants, as evidenced by an increase in the AtD50 of M, DC and DX. p-Chlorophenylalanine (PCPA; 300 mg/kg, 24 hr) specifically produced a reduction of more than 70% in the level of 5-HT in the brain. The PCPA-treated rats also displayed an inhibition of the antitussive effect. The AtD50 in reserpine- and PCPA-treated rats was 2- and 4-fold higher, respectively, than the AtD50 for normal rats. alpha-Methyl-p-tyrosine (300 mg/kg, 5 hr) produced a significant reduction in the levels of NE and DA in the brain, but the antitussive effects of M, DC and DX were not altered. These results suggest that 5-HT in the brain may play an important role in the mechanism of action of antitussive drugs.
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PMID:Monoamines and the mechanisms of action of antitussive drugs in rats. 296 57

Diet clearly influences neurotransmission. This can be important in grossly undernourished children. It can also be important in children in whom normal homeostatic mechanisms governing food intake are bypassed. Subtle differences in behavior can occur with physiologic variation in food intake. Components of foods can also be used as drugs. Starvation can impair neuronal maturation and can have lasting effects upon behavior and intellectual performance. The extent of starvation's impact upon the brain depends upon whether undernutrition occurred during a critical phase in brain development. Short-term fasting has small, but significant, effects upon intellectual performance. Even when gross malnutrition is not present, subtle changes in diet may modulate brain function. Tryptophan, tyrosine, and choline in the diet are used as precursors for neuronal synthesis of serotonin, dopamine and norepinephrine, and acetylcholine, respectively. It is likely that the brain's sensitivity to certain components of the diet exists to permit monitoring of food intake by the central nervous system. Tryptophan, tyrosine, and choline may be useful in treatment of humans with sleep disorders, pain depression, mania, hypertension, shock, or dyskinesias. Other components of the diet that may affect behavior include food additives, sugar, and caffeine. Food additives may exacerbate hyperactive symptoms in a small proportion of children with attention deficit disorder. Given that there is little potential for harm and that there is a subpopulation that may respond, a trial of a diet that contains no food additives may be a valid diagnostic approach for children with attention deficit disorder who do not respond to stimulant therapy or for children for whom stimulant therapy is not desired. Refined sugar has been blamed for many behavioral abnormalities. Subtle effects of carbohydrate upon behavior have been reported, but the existing data do not support the hypothesis that sucrose or fructose exert special effects upon neurotransmission. Caffeine is easily detected as a stimulant by humans, but it has little effect upon cognitive function. Administration of large doses of vitamins has no beneficial effect in most humans with schizophrenia, attention deficit disorder, autism, Down's syndrome, or drug addiction. Large doses of niacinamide may even be harmful, as they may cause hepatic damage.
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PMID:Dietary influences on neurotransmission. 302 51

Pretreatment plasma ratios of tryptophan (Trp) and tyrosine (Tyr) to other large neutral amino acids were determined in 27 depressed patients who completed a double-blind trial of citalopram, a selective serotonin uptake inhibitor, against maprotiline, a selective noradrenaline uptake inhibitor. The Trp ratio and the Tyr ratio were decreased in the total patient sample as compared with healthy controls. Plasma Tyr ratio was normal in the endogenous, but significantly decreased in the non-endogenous depressives. There was no significant relationship between the plasma Trp ratio and the probenecid-induced accumulation of 5-HIAA in the CSF, or between the plasma Tyr ratio and HVA level in CSF, whereas the CSF level of MHPG correlated significantly with the plasma Tyr ratio. There was a significantly positive correlation between the Trp ratio, the Tyr ratio, their sum and the final Hamilton depression score in 14 patients treated with citalopram; on the whole, this association was evident also in the endogenous and non-endogenous subgroups. In 13 patients on maprotiline there was a significantly positive correlation between the plasma Tyr ratio and the percent reduction of Hamilton depression score; this association was poor in the endogenous, whereas a trend towards a correlation remained in the non-endogenous subgroup. The results suggest that the plasma Trp and Tyr ratios may be determinants of clinical improvement in depressed patients to treatment with citalopram and maprotiline. However, further studies are needed on larger patient samples to allow a firm conclusion.
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PMID:Plasma tryptophan and tyrosine ratios to competing amino acids in relation to antidepressant response to citalopram and maprotiline. A preliminary study. 308 Jul 81

Twelve patients with polysommographic and clinical signs of dopamine-dependent depression (DDD) received, after a short-lasting trial with the dopamine agonist Piribedil, a treatment with oral-tyrosine (3,200 mg/day). On the very first day of treatment a return to mood, as judged by clinical impression and MADRS scores was observed. Sleep recordings performed on nights following days 1, 2, 7 and 8 of treatment showed an immediate improvement of those sleep parameters differentiating the more clearly DDD from other types of depression. More than 50 patients have now been treated successfully for periods ranging from a few months to almost 2 years. This treatment is ineffective in other types of depression.
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PMID:[L-tyrosine cures, immediate and long term, dopamine-dependent depressions. Clinical and polygraphic studies]. 312 95

The effects of decreased food intake and degree of surgical trauma on total, myofibrillar and sarcoplasmic muscle protein synthesis and degradation were assessed in two experiments (A and B). Trauma consisted of an abdominal incision with or without hysterectomy. The degree of trauma in experiment B was increased relative to that in experiment A by extending the length of the incision, operative manipulation and time required to perform the surgery. To account for postoperative diminutions in food intake on protein turnover, a group of nonoperated rats were pair-fed to the level of food consumed by hysterectomized rats. Traumatized rats in experiment B lost more weight, ate less, and had a lower muscle total protein concentration than corresponding rats in experiment A, confirming a more severe trauma in experiment B. In both experiments, trauma depressed total protein content of muscle. Synthesis was measured by the incorporation of L-[U-14C] tyrosine from a single meal into total, sarcoplasmic and myofibrillar proteins of gastrocnemius muscle. Degradation was calculated as the difference between the growth rate and the synthetic rate. Synthetic rate (ks) of total protein was depressed by surgical trauma; the more severe the trauma, the greater the depression. In mild trauma, the depression in ks was due only to a decrease in sarcoplasmic protein synthesis (ke), whereas with more severe trauma, synthetic rates of both sarcoplasmic (kes) and myofibrillar (kem) proteins were decreased. Protein degradation (kd,) was increased on day 2 in experiments A and B, had returned to control values on day 4 in experiment A and had decreased below control values in experiment B.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Muscle protein metabolism of rats in surgical trauma. 318 21

Rats were trained to eat a 6% casein basal diet during a 3-hour period per day. They were then fed either the same 6% casein diet or a 44% casein diet for 3 hours. No food intake depression was observed in the rats eating 44% casein diet during the 3-hour period. Plasma ammonia and amino acids and brain amino acids were measured at 0, 4, 12 and 24 hours after presentation of the 6% or 44% casein diets. Plasma ammonia rose to 134 (p less than 0.01) and 110 micromolar (p less than 0.05) in the 44% casein fed rats at 4 and 12 hours, respectively, as compared to 67 and 53 micromolar, respectively, for the 6% casein fed rats. All plasma amino acid concentrations except methionine and glutamate were elevated (p less than 0.05) at 4 hours. In the brain, threonine, glutamine and tyrosine concentrations were elevated (p less than 0.05) at 4 hours after diet presentation. At 24 hours, valine, isoleucine, leucine, phenylalanine, and methionine concentrations were also elevated (p less than 0.05). Because intake of the 44% casein diet decreases the second day of its presentation, as noted in an earlier experiment, the increases in plasma ammonia and its possible entry into the brain as reflected by increased brain glutamine together with changes in amino acid concentrations should be considered collectively among possible metabolic signals affecting intake of high protein diets.
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PMID:Increase in plasma ammonia and amino acids when rats are fed a 44% casein diet. 320 Sep 19


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