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)

Levamisole at concentrations of 10(-3) M or 10(-4) M consistently increased neutrophil random motility and chemokinesis (stimulated random migration). Similar concentrations also increased directional movement of polymorphonuclear leukocytes to both endotoxin-activated serum and hydrolyzed casein. This effect on chemotaxis was due to a true stimulation and was not due solely to increased random movement. The effect of levamisole on the neutrophils could be removed by washing, but persisted if the cells were initially treated with levamisole and serum or endotoxin-activated serum. After neutrophil stimulation with chemotactic factor an initial rise in intracellular cyclic AMP levels was detected which was not influenced by prior levamisole treatment. Intracellular cyclic GMP levels after an initial slight depression, returned to resting levels and gradually diminished over a 60-minute period. Levamisole-treated cells consistently showed higher cyclic GMP levels and it is postulated that by maintaining intracellular cyclic GMP levels, microtubular assembly and cell motility might be enhanced.
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PMID:In vitro stimulation of neutrophil motility by levamisole: maintenance of cgmp levels in chemotactically stimulated levamisole-treated neutrophils. 18 91

Insulin accelerates the entry of glucose and amino acids into muscle cells by acting upon the 'carrier-facilitated' transport mechanism. For glucose this process is passive and leads to equilibration of intracellular and extracellular concentrations. In heart muscle, glucose transport is a rate-limiting step for glucose uptake. During hypoxia and ischemia the heart turns to anaerobic glycolysis for energy production and therefore, maximal glucose transport becomes important. Insulin is necessary to insure proper protein synthesis, probably at the level of membrane-bound polyribosomes. However, during myocardial hypoxia, insulin alone cannot restore the associated depression in protein synthesis. Although insulin hyperpolarizes the cell, a change in the ratio of intracellular to extracellular activities of potassium is not its primary mode of action. An insulin-induced configurational change in the plasma membrane could simultaneously account for the effects of insulin on sodium and potassium permeability and the action on facilitated transport. Intracellular levels of cyclic adenylate may be reduced by insulin in adipose tissue because of inhibition of adenyl cyclase or stimulation of phosphodiesterase. However, at this time there is little evidence that insulin alters cyclic AMP levels in the heart. Insulin secretion is depressed in patients with heart disease in proportion to the reduction of cardiac index sustained. Since the ischemic heart is dependent upon glucose as the major fuel, insulin lack may deprive the heart of adequate substrate.
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PMID:Insulin: fundamental mechanism of action and the heart. 18 67

Vasopressin increases the permeability of the total urinary bladder, an analogue of the mammalian renal collecting duct, to water and small solutes, especially the amide urea. We have observed that three general anesthetic agents of clinical importance, the gases methoxyflurane and halothane and the ultrashortacting barbiturate methohexital, reversibly inhibit vasopressin-stimulated water flow, but do not depress permeability to urea, or the the lipophilic solute diphenylhydantoin. In contrast to their effects in vasopressin-treated bladders, the anesthetics do not inhibit cyclic AMP-stimulated water flow, consistent with an effect on vasopressin-responsive adenylate cyclase. The selectivity of the anesthetic-induced depression of water flow suggests that separate adenylate cyclases and cyclic AMP pools may exist for control of water and urea permeabilities in to toad bladder. Furthermore, theophylline's usual stimulatory effect on water flow, but not its effect on urea permeability, was entirely abolished in methoxyflurane-treated bladders, suggesting that separate phosphodiesterases that control water and urea permeabilities are present as well. We conclude that the majority of water and urea transport takes place via separate pathways across the rate-limiting luminal membrane of the bladder cell, and that separate vasopressin-responsive cellular pools of cyclic AMP appear to control permeability to water and to urea.
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PMID:Selective inhibition of osmotic water flow by general anesthetics to toad urinary bladder. 18 13

1. In the present experiments evidence was shown which demonstrates that PGF2alpha treatment of the rat produces a rapid fall in circulating progesterone in the latter part of pseudopregnancy but not shortly after corpus luteum formation. This refractory period of at least 3 days following ovulation is similar to that which occurs in large animals, such as the cow. 2. Loss of luteal LH receptors was associated with a loss in LH-stimulated progesterone synthesis and an attenuation of LH-stimulated cyclic AMP synthesis in vitro, a finding which supports a functional loss of LH activity in such tissues exposed in vivo to PGF2alpha. Tissue levels of cyclic GMP were generally decreased by both LH, PGF2alpha, and incubation and the relevance of the latter cyclic nucleotide remains obscure in luteolysis and corpus luteum function. 3. The depression of progesterone induced by PGF2alpha precedes a marked drop in corpus luteum LH receptors but no change in reeptor affinity was seen. For example, the first significant drop in LH receptors was observed 8 hr after PGF2alpha treatment whereas serum progesterone was depressed within 2 hr. 4. Prolactin administration to animals simultaneously with PGF2alpha blocked the loss in LH receptors and serum progesterone observed with PGF2alpha treatment alone. In one experiment, but not in the other, prolactin treatment alone produced an elevation in corpus luteum LH receptors. Suppression of endogenous prolactin secretion with ergocryptine mimicked the effect of PGF2alpha on both the LH receptor and serum progesterone and this effect was also blocked with simultaneous prolactin treatment. It is concluded that the mechanism of PGF2alpha-induced luteolysis has several components. The initial event appears to be due to direct gonadotropin antagonism which occurs independently from a change in quantity of luteal LH receptors. This effect has been shown in vitro (10) as well as in vivo (3) and the mechanism appears not to be related to changes in ovarian hemodynamics and not to direct antagonism of LH binding to its receptor (23). Possibly the early effect of PGF2alpha may be due to elevation of cGMP which then antagonizes cyclic AMP action, but our studies to date have been unsuccessful in demonstrating such a response. Eight hours following PGF2alpha administration, the first measurable decrease in LH receptors was seen and this response was correlated with the first sign of functional luteolysis, elevation of serum 20alpha-ol. The latter response is correlated with a loss of prolactin action on the corpus luteum; it was therefore interesting to observe that prolactin blocked, and ergocryptine mimicked, the PGF2alpha effect on the LH receptor and serum progesterone. Thus, one is lead to the conclusion that the mechanism of luteolysis produced by PGF2alpha in the rat is closely associated with a loss in prolactin activity...
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PMID:Studies on the mechanism of PGF2alpha and gonadotropin interactions on LH receptor function in corpora lutea during luteolysis. 18 87

beta-Adrenoceptor function has been compared in lymphocytes of normal subjects, asthmatic patients taking large doses of beta-adrenergic bronchodilators, and comparable asthmatics treated exclusively with nonadrenergic medication. The effect of prolonged administration of beta-adrenoceptor agonists on receptor function in normal subjects has also been examined. beta-receptor response in each situation was quantitated by changes in levels of cyclic AMP, measured by a protein-binding assay. Dose response curves to isoproterenol (10 nM-0.1 mM) have been constructed for each group. Maximal increase in cyclic AMP in lymphocytes from normal subjects (393.2+/-44.0%) and in asthmatics on nonadrenergic preparations (408.3+/-46.7%) was significantly greater (P less than 0.001) than in asthmatics taking large doses of beta-sympathomimetics (67.5+/-24.2%). Depression of the cyclic AMP response appeared to correlate with the degree of exposure to beta-adrenergic agonists but not with the prevailing severity of the patient's asthma. Withdrawal of beta-adrenergic drugs was followed by a reversion of the cyclic AMP response to normal values, which suggests that the depression was drug-induced rather than an inherent feature of the disease. This interpretation was confirmed by the finding that prolonged exposure of normal subjects to high doses of a beta-adrenergic agonist caused a marked and significant (p less than 0.001) reduction in the cyclic AMP response, very similar to that seen in asthmatics on large doses of adrenergic bronchodilators. A possible link between drug-induced changes in the cyclic AMP response and the rise in the United Kingdom asthma death rate in the 1960's is discussed.
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PMID:The lymphocyte beta-adrenoceptor in normal subjects and patients with bronchial asthma: the effect of different forms of treatment on receptor function. 18 88

The effects of chronic oral ingestion of lead in doses ranging from 20-80 ppm were compared with those seen after the subacute exposure of rats to a 10 mg/kg daily dose of the heavy metal for 7 days. Irrespective of the treatment regimen used, lead treatment significantly increased the activities of renal pyruvate carboxylase, phosphoenolpyruvate carboxykinase, fructose 1,6-diphosphatase and glucose 6-phosphatase. The observed enhancement of kidney gluconeogenic enzymes in chronically treated animals was associated with a stimulation of the adenylate cyclase-cyclic AMP system, a rise in blood blucose and urea as well as a depression in hepatic glycogen and serum immunoreactive insulin (IRI) levels. In contrast, subacute exposure to lead failed to significantly alter cyclic AMP metabolism and the concentrations of liver glycogen, blood glucose, serum urea or IRI. Whwereas the insulinogenic index (the ratio of serum IRI to blood glucose concentration) was markedly suppressed in chronically treated rats, this ratio remained within normal limits following subacute exposure to the heavy metal. However, a marked decrease in the insulinogenic index was observed in subacutely treated rats 15 min after the administration of a glucose load. The data provide evidence to show that increased glucose synthesis as well as suppressed pancreatic function may be responsible for lead-induced disturbances in glucose homeostasis.
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PMID:Effects of subsacute and chronic lead treatment on glucose homeostasis and renal cyclic AMP metabolism in rats. 18 14

The effects of mannoheptulose and DL-glyceraldehyde on glucose-induced insulin release and cycli AMP levels in islets isolated from rat pancreas were investigated. Mannoheptulose inhibition on glucose-induced insulin release was observed after only 5-min incubation period, indicating an inhibitory effect on the early phase of insulin release. This inhibition on insulin release was accompanied with the simultaneous depression of cyclic AMP levels in islets. By the addition of DL-glyceraldehyde to the medium in which glucose and mannoheptulose were present, the depressed cyclic AMP levels in islets were recovered to the control level completely but the restoration of insulin release in the early phase was not complete. In the absence of glucose, DL-glyceraldehyde did not demonstrate a significant increase of insulin release during 5 min incubation, though a marked stimulation was observed after 30-min incubation. Cyclic AMP levels in islets were not affected by DL-glyceraldehyde. When DL-glyceraldehyde was added to the medium with glucose, significant inhibition of glucos-induced insulin release in its early phase was observed without the reduction of cyclic AMP levels in islets. From these findings, the following possibilities are suggested and discussed. 1. Maintenance of the cyclic AMP levels in islets is a necessary but insufficient condition for glucose-induced insulin release particularly for its early phase. 2. Glucose-induced insulin release seems to depend on both the binding of glucose with glucoreceptor and the supply of some metabolites. Mannoheptulose inhibits both mechanisms. DL-glyceraldehyde may supply metabolites but competitively inhibit the binding of glucose to the glucoreceptor.
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PMID:Effects of mannoheptulose and DL-glyceraldehyde on glucose induced insulin release and adenosine 3',5'-monophosphate levels in isoalted islets of rat pancreas. 18 34

Follicular cells isolated from normal human thyroid tissue have been cultured for up to 140 h with bovine thyrotrophin (TSH) or dibutyryl cyclic AMP (DBcAMP). Both compounds induced marked reorganization of the cells into three-dimensional follicular structures, whilst non-supplemented cells assumed a monolayer form. Cultures treated initially with TSH or DBcAMP showed a greater iodide uptake capacity, in comparison with unsupplemented cultures, in which iodide uptake was markedly diminished after 24 h. The release of tri-iodothyronine (T3) and thyroxine (T4) into the medium was determined by radioimmunoassay. Both TSH- and DBcAMP-treated cells showed a significant increase in iodothyronine output compared with unsupplemented control cells. In contrast to the "classical" TSH-induced depression of the T4:T3 ratio in vivo, an increase in the ratio was observed for both TSH- and DBcAMP-supplemented cells in vitro. The ratio was also significantly greater after TSH than after DBcAMP, and possible implications of this findings are discussed.
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PMID:In-vitro studies of normal human thyroid cells: responses to thyrotrophin and dibutyryl cyclic AMP. 18 67

Stimulated rabbit peritoneal polymorphonuclear leukocyte (PMN) preparations simultaneously produce prostaglandin-like material and mediators that induce metabolic alterations in experimental animals characteristic of the host's responses to inflammation. The alterations observed in rats include responses by: proteins, carbohydrates, hormones, trace metals, and total blood neutrophils. This study demonstrates a possible relationship between prostaglandins and PMN-derived substances that mediate plasma zinc depression, hepatic amino acid uptake, and increased numbers of blood neutrophils. Production of these mediators by stimulated-PMN preparations was prevented by 23 muM indomethacin or 93 muM aspirin. Conversely, morphine (2 mM or less) had no detrimental effect on production of these mediators, although, it consistently stimulated production of a substance stimulating total blood neutrophia. In addition, 2 muM prostaglandin E and F stimulated production of substances mediating hepatic amino acid uptake plasma zinc depression, respectively. At this concentration, neither prostaglandin significantly altered production of substances mediating increased numbers of total blood neutrophils. A partial-nitrogen atmosphere, dibutyryl cyclic analogs of AMP and GMP, or homogenization of the PMN had no effect on mediator production. The inhibitory effect of indomethacin and aspirin also was observed with PMN-homogenastes. These experimental observations suggest that prostaglandin synthesis has a function in production of mediators by stimulated-PMN preparations.
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PMID:Possible relation of prostaglandins to PMN-derived mediators of host metabolic responses to inflammation. 19 Jun 50

The daily excretion of adenosine 3'5' cyclic monophosphate (c-AMP) in a group of 19 patients with a severe depressive illness was found to be significantly decreased when compared with that from a group of euthymic patients being treated for other disorders in the same ward. The daily excretion of the depressed patients increased during the period of treatment and recovery from the illness. Treatment with a tricyclic antidepressant caused a greater increase than electroconvulsive treatment (ECT). There was no difference between the mean plasma c-AMP concentration of the depressed and euthymic groups. The mean CSF-c-AMP concentration was not different from the mean plasma c-AMP concentration in 12 patients with severe depression. There was no direct correlation between the CSF and plasma concentrations within patients. It was concluded that there may be a reversible disturbance in the renal metabolism of c-AMP in patients with severe depression.
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PMID:Adenosine 3'5' cyclic monophosphate metabolism in patients with severe depressive illness. 19 39


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