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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects on GH and PRL secretion of several pharmacological agents known to modify central neurotransmitter action were determined in unanesthetized male rats. Phenoxybenzamine, an alpha-adrenergic blocker (5 mg/kg iv), abolished episodic GH secretion and caused elevation of serum PRL levels. Propranolol, a beta-adrenergic blocker (5 mg/kg iv), had no effect on GH secretion and caused a small but significant depression in PRL levels. Parachlorophenylalanine methyl ester, an inhibitor of tryptophan hydroxylase (300-350 mg/kg ip), resulted in significant inhibition of GH pulsatile secretion and suppressed PRL levels. Methysergide hydrogen maleinate (25 mg/kg iv), a serotonin receptor antagonist, also inhibited GH secretion, but produced a transient stimulation in PRL levels. Atropine sulfate (2 mg/kg iv) caused significant suppression in GH secretion, but had no effect on PRL. Picrotoxin, a gamma-aminobutyric acid antagonist, in a subconvulsive dose of 1-3 mg/kg iv, also depressed GH episodic secretion but did not affect PRL levels. These results indicate that several neurotransmitters, i.e., norepinephrine, serotonin, acetylcholine, and gamma-aminobutyric acid, found in high concentration in the hypothalamus, influence GH and PRL secretion.
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PMID:Neuropharmacological regulation of episodic growth hormone and prolactin secretion in the rat. 3 92

Respiration and glycolysis of pig platelets suspended in a dialyzed plasma were studied at various hydrogen ion concentrations. Respiration of platelets was high at acidic pH and decreased at physiological pH. This pH profile may not be attributed to properties of mitochondria, since the respiratory rate of mitochondria prepared from platelets was maximal at physiological pH. A low respiratory rate at physiological pH seemed to be attributable to depression of respiration by glycolysis, since the addition of glucose further depressed the rate. The Crabtree effect was more prominent at alkaline ph. glycolysis increased with an increase in the pH of the plasma, contrary to oxygen comsumption. The Pasteur effect was less prominent at alkaline pH. The effect of pH on lactate production by the cytosol fraction of platelets was similar to that of whole platelets. The glycolytic intermediate pattern showed that phosphofructolinase was the committed step. Both ATP concentration and ATP formation calculated from respiratory and glycolytic rates were constant at various pH values. These observations may indicate that the pH primarily affects platelet glycolysis at the phosphofructokinase step and the respiration is secondarily controlled by glycolysis.
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PMID:Effect of hydrogen ion concentration on energy metabolism in pig platelets. 23 23

The trace metals nickel and platinum, which are not substrates for ferrochelatase and thus do not form heme in biological systems, were found to act similaryl to cobalt, and heme itself, in regulating heme metabolism in liver and kidney. These metals induced heme oxygenase activity in both organs with the peak of induced enzyme activity reached approximately 16 hr after single injections in rats. Both metals caused transient depression of cellular glutathione content followed by increases above normal after 12 hr in liver. Nickel and platinum were more potent inducers of heme oxygenase in kidney than in liver (10-13 times normal versus 5-6 times normal). At high concentrations, they inhibited heme oxygenase [heme, hydrogen-donor:oxygen oxidoreductase (alpha-methene-oxidizing, hydroxylating), EC 1.14.99.3] in vitro. Both were active in regulating heme metabolism only when administered in the ionic form. Complexing of the metals with sulfhydryl agents completely blocked their actions on heme metabolism. Administration of cysteine orally prior to or shortly after administration of the metals had a similar blocking effect. Nickel and platinum produced depression of delta-aminolevulinate synthase [succinyl-CoA:glycine c-succinyltransferase (decarboxylating), EC 2.3.1.37] activity in liver, but neigther inhibited this rate-limiting ennzyme for heme synthesis in vitro. Furthermore, despite the substantial decreases in cellular heme and hemoprotein contents mediated by the metal, production of delta-amimolevulinate synthase did not undergo the compensatory increase that would be expected if there were a direct reciprocal feedback relationship between cellular heme level and synthesis of this enzyme. These findings indicate that it is not necessary for metal ions to be chelated in the porphyrin ring in order to regulate the enzymes of heme synthesis and heme oxidation. Accordingly, it is suggested that the iron atom of heme is the proximately active regulator of delta-aminolevulinate synthase and heme oxygenase--actions generally ascribed to the iron-tetrapyrrole complex itself--and that the tetrapyrrole moiety of the complex functions primarily as a means of transport of the metal to regulatory sites in cells.
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PMID:Regulation of heme pathway enzymes and cellular glutathione content by metals that do not chelate with tetrapyrroles: blockade of metal effects by thiols. 26 10

1. Mongrel dogs were anaesthetized with chloralose, paralysed, ventilated and vagotomized and given a beta-blocking drug, sotalol, in sufficient doses to block the effects of 5 microgram of adrenaline. 2. Changes in inspired CO2 concentration were produced, causing increases of arterial PCO2 up to 120 mmHg. The effects on myocardial blood flow were measured with radioactive microspheres. Coronary sinus and arterial blood was sampled. 3. In the absence of beta-blockade, an increase in arterial PCO2 produced variable effects. In some dogs coronary blood flow increased, while in others there was no change. There was a mean increase in coronary blood flow at arterial PCO2 values above 85 mmHg which was abolished by beta-blockade. 4. In the presence of beta-blockade, an increase of arterial PCO2 produced depression of left ventricular performance, i.e. a fall of maximum rate of rise of left ventricular pressure and a rise of left ventricular end-diastolic pressure. 5. In the presence of beta-blockade, there were no consistent changes in myocardial blood flow, left ventricular pressure or cardiac output. 6. In the absence of beta-blockade, coronary arterial minus venous ocygen content was reduced by hypercapnia. In the presence of beta-blockade, the changes were small and not statistically significant. The direct coronary vasodilator effect was therfore negligible. 7. It is concluded that the previously reported hypercapnic vasodilatation was mainly an effect of sympatho-adrenergic stimulation by hypercapnia. 8. In the presence of beta-blockade, coronary sinus PO2 increased markedly, with little change in coronary sinus oxygen content; this was consistent with a shift to the right of the oxy-haemoglobin dissociation curve. Under circumstances of hypercapnia, a rise in coronary sinus (and presumably tissue) PO2 failed to produce vasoconstriction. 9. It is argued that the vasodilator effect of hydrogen ions and the vasoconstrictor effect of oxygen probably cancel one another when the arterial PCO2 is raised.
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PMID:The effect of carbon dioxide upon myocardial contractile performance, blood flow and oxygen consumption. 43 Mar 87

The effects of ketamine and barbiturates (pentobarbital, thiopental, methohexital) were studied in an isolated rabbit Langendorff preparation. All agents tested depressed contractility. Ketamine, as well as the lipophilic barbiturates (thiopental, methohexital), caused a relatively greater depression at higher pacing rates such that the force-frequency relation was reversed. Pentobarbital did not reverse Bowditch. The effects of barbiturates on Bowditch correlated directly with lipid solubility, suggesting that their rate-related effects are due to perturbation of the membrane lipid bilayer. Disruption of hydrogen bands between polar membrane components may also be involved. The time course of the effect of thipental at high pacing rates was slower, both in onset and recovery, than at low rates. At a pacing rate of 1 Hz, maximal depression of contraction developed within 5 min. However, at 2.5 Hz, contractility continued to decline for up to 30 min. After 5 min of perfusion with thiopental, Bowditch was still positive, but by 30 min it was reversed. These temporal differences in thipental effects suggest that different mechanisms may dominate in the support of contractility at different ranges of heart rate.
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PMID:Effects of barbiturate anesthetics and ketamine on the force-frequency relation of cardiac muscle. 51 Apr

The possibility of using a fluorescent probe technique for the study of drug-providone (I) interactions was investigated. 1-Anilino-8-naphthalenesulfonate (II) was used as the probe. Sulfanilamide, sulfacetamide, and sulfabenzamide were used as the binding competitors. Both sulfacetamide and sulfabenzamide decreased the fluorescence intensity of the I-II complex, while sulfanilamide increased the intensity. The fluorescence depression was greater with sulfabenzamide than with sulfacetamide, indicating that the former is more strongly bound to povidone. Since sulfabenzamide has a greater hydrophobic group (phenyl) than sulfacetamide (methyl), the binding of these sulfonamides to povidone is probably at least partially hydrophobic in nature. The enhanced fluorescence intensity of the I-II complex in the presence of sulfanilamide is believed to involve hydrogen bonding in which the sulfanilamide acts as an intermediary between I and II. Double reciprocal plots for the I-II and sulfonamide-I interactions were employed to obtain a binding constant of 3.2 X 10(4) M-1 for the I-II interaction. The association constants for sulfacetamide and sulfabenzamide were calculated by means of the Klotz equation to be 13.4 and 56.8 M-1, respectively. The povidone molecules appear to have 1.28 binding sites for these compounds under the experimental conditions.
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PMID:Fluorescent probe study of sulfonamide binding to povidone. 89 4

Lisuride hydrogen maleate induced stereotyped behaviour in normal as well as in reserpinized mice. It antagonized the motor depression and hypothermia induced by reserpine. On i.p. administration the compound was about as effective as apomorphine and D-amphetamine. As with apomorphine and in contrast to D-amphetamine the effects of lisuride hydrogen maleate in reserpinized mice were not impaired by additional treatment with alpha-methyl-p-tyrosine methylester. In untreated mice, the substance was very potent in lowering body temperature with significant hypothermia measured after dosages as low as 0.10 mg/kg i.p. Occurrence of stereotyped behaviour and hypothermia could be prevented by the dopaminergic antagonist haloperidol. From these data it is concluded that lisuride hydrogen maleate in addition to its interaction with serotoninergic systems is a potent dopaminergic agonist with a probably direct action on dopaminergic receptors. Further arguments in support of such an action of lisuride hydrogen maleate are, in addition to biochemical data, its serum prolactin lowering effect in rats, its strong emetic action in dogs and its effects on rat behaviour.
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PMID:Direct dopaminergic action of lisuride hydrogen maleate, an ergot derivative, in mice. 94 66

Raman spectroscopy was used to study the anomalous decrease in the freezing temperature of water produced by an antifreeze glycoprotein obtained from the sera of an Antarctic fish. An active fraction of this glycoprotein has a molecular weight of approximately 18,000 by equilibrium sedimentation compared to an apparent weight of 20 by freezing temperature depression. The Raman spectra of water present in a 1% antifreeze glycoprotein solution and of ice frozen from this solution were indistinguishable from the spectra of pure water and ice, respectively. These results indicate that the bulk properties of water and ice are unaffected by the presence of the antifreeze glycoprotein. Raman measurements on ice grown slowly, using as seed an oriented single crystal of ice in contact with 1% glycoprotein solutions, showed that the active glycoprotein was not excluded from the ice phase. On the other hand, we found that a smaller, inactive glycoprotein was excluded. Comparison of the Raman spectra of active and inactive glycoprotein components as solids, in 5% solutions, and rapidly frozen 5% solutions, showed that the two components differ in conformation and possibly in the environment of their carbohydrate hydroxyls. These observations suggest that hydrogen bonding of the carbohydrate hydroxyls of the active glycoprotein at the ice-solution interface may physically prevent growth of the ice lattice.
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PMID:Raman spectra of a solid antifreeze glycoprotein and its liquid and frozen aqueous solutions. 126 26

Potassium is tightly regulated within the extracellular compartment of the brain. Nonetheless, it can increase 3- to 4-fold during periods of intense seizure activity and 10- to 20-fold under certain pathological conditions such as spreading depression. Within the central nervous system, neurons and astrocytes are both affected by shifts in the extracellular concentration of potassium. Elevated potassium can lead to a redistribution of other ions (e.g., calcium, sodium, chloride, hydrogen, etc.) within the cellular compartment of the brain. Small shifts in the extracellular potassium concentration can markedly affect acid-based homeostasis, energy metabolism, and volume regulation of these two brain cells. Since normal neuronal function is tightly coupled to the ability of the surrounding glial cells to regulate ionic shifts within the brain and since both cell types can be affected by shifts in the extracellular potassium, it is important to characterize their individual response to an elevation of this ion. This review describes the results of side-by-side studies conducted on cortical neurons and astrocytes, which assessed the effect of elevated potassium on their resting membrane potential, intracellular volume, and their intracellular concentration of potassium, sodium, and chloride. The results obtained from these studies suggest that there exists a marked cellular heterogeneity between neurons and astrocytes in their response to an elevation in the extracellular potassium concentration.
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PMID:Effect of elevated potassium on the ion content of mouse astrocytes and neurons. 129 76

Twelve ergolines (O-acylated lysergol and dihydrolysergol-I derivatives) were synthesized to study their antagonism of 5-HT responses in comparison with methylsergide and LY 53857 [6-methyl-1-(1-methylethyl)-8 beta-ergoline carboxylic acid 2-hydroxy-1-methylpropyl-ester hydrogen maleate] in cylindrical segments of the isolated rat tail artery. With regard to (9.10-didehydro-6-methyl-8 beta-ergoline)methyl R,S-2-methylbutyrate, the most potent new ergoline derivative, we examined the phenomenon of insurmountable antagonism to 5-HT by methylsergide. O-Acylated lysergol and dihydrolysergol-I derivatives competitively antagonized 5-HT-induced contractions with calculated pA2 values of 7.30 +/- 0.42 for the weakest and 8.42 +/- 0.35 for the most potent ergoline derivative in this series. N1-isopropyl substitution did not generally enhance 5-HT2 receptor affinities but lowered affinities for alpha 1 adrenoceptors in rat aorta. Methysergide and LY 53857 were insurmountable antagonists of 5-HT in rat tail artery. Preincubation with (9.10-didehydro-6-methyl-8 beta-ergoline)methyl R,S-2-methylbutyrate (1 mumol/l) partially prevented the depression of 5-HT-induced contractions caused by methysergide (1-10 nmol/l). Methysergide (100 nmol/l) abolished the protective effect of (9.10-didehydro-6-methyl-8 beta-ergoline)methyl R,S-2-methylbutyrate. (9.10-Didehydro-6-methyl-8 beta-ergoline)methyl R,S-2-methylbutyrate (1 mumol/l), concomitantly incubated with methysergide (30 nmol/l), partially restored the maximum response to 5-HT that had been depressed by methysergide (30 nmol/l). Partial restoration could not be mimicked by washout of methysergide.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:O-acylated lysergol and dihydrolysergol-I derivatives as competitive antagonists of 5-HT at 5-HT2 receptors of rat tail artery. Allosteric modulation instead of pseudoirreversible inhibition. 132 Feb 7


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