Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cyclic GMP depresses Ba2+ current through high-voltage-activated Ca2+ channels (ICa) in acutely isolated hippocampal neurons. The effect is produced by intra-, but not extracellular, cGMP or by 5' GMP. The membrane-permeant derivative, 8-Br-cGMP, produces a reversible suppression. The effect of 8-Br-cGMP is similar to phorbol ester-induced ICa depression, except that ICa depression due to 8-Br-cGMP is not blocked by protein kinase inhibitors H-8 or H-7, whereas phorbol ester effects are. The data suggest that cGMP depresses ICa by a cGMP-kinase- and protein kinase C (PKC)-independent mechanism. Cyclic AMP, which enhances ICa, and the cyclic nucleotide phosphodiesterase inhibitor, IBMX, both antagonize ICa depression induced by 8-Br-cGMP, but not that due to phorbol esters. Cyclic IMP, a more potent activator of phosphodiesterase than of cGMP-dependent protein kinase, is also a powerful depressant of ICa. We conclude that cGMP-induced depression of ICa is mediated by activation of cyclic nucleotide phosphodiesterase with consequent reduction of intracellular cAMP.
 ...
PMID:Cyclic GMP depresses hippocampal Ca2+ current through a mechanism independent of cGMP-dependent protein kinase. 285 1

Isonicotinic hydrazide, a drug that decreases the level of GABA, when injected subcutaneously in control and scrapie-infected hamsters induced tonic-clonic seizures in scrapie hamsters significantly earlier (P less than 0.0001) than in control animals. This suggests depression of the GABAergic system in scrapie-infected hamsters. To determine whether this lesion is pre or postsynaptic we measured the level of GABA, glutamate, cGMP and cAMP and the GABA-benzodiazepine receptor complex.
 ...
PMID:Isonicotinic hydrazide causes seizures in scrapie-infected hamsters with shorter latency than in control animals: a possible GABAergic defect. 285 87

The present study examined changes in the levels of plasma catecholamines and myocardial histamine, guanylate cyclase activity, cyclic nucleotides, calcium, calmodulin, and norepinephrine following chronic administration of doxorubicin (DXR). In addition, changes in myocardial alpha 1-adrenergic receptor density and dissociation constant were measured. Rats received DXR (2 mg/kg) or vehicle weekly by the SC route for 2, 4, 8, and 13 weeks. Rats were sacrificed one week after their last dose. One group of rats treated for 13 weeks was sacrificed at 19 weeks, six weeks after the last dose. Heart histamine was unchanged at 3, 5, 9, and 19 weeks, yet at 14 weeks it was significantly elevated in DXR-treated rats over controls. Cardiac calcium, norepinephrine, and cyclic GMP levels were unchanged throughout the course of the study. Cardiac cAMP and calmodulin levels were unchanged at 3, 5, 9, and 14 weeks. At 19 weeks in DXR-treated rats, cAMP was depressed while calmodulin was elevated. Plasma catecholamines and myocardial guanylate cyclase activity examined at 14 weeks were unchanged. In contrast, alpha 1 receptor density examined at 14 weeks in DXR-treated rats was significantly depressed while the dissociation constant was unchanged. Changes in cAMP and calmodulin are suggestive of a redistribution of calcium, although total levels of calcium were unchanged. The depression of cAMP indicates damage to the membrane bound enzyme, adenylate cyclase, and that the membrane interaction of doxorubicin appears to be an integral part of the biochemical mechanism of its toxicity.
 ...
PMID:Effects of chronic administration of doxorubicin on myocardial alpha-adrenergic receptors, histamine, cyclic nucleotides, calcium, norepinephrine, calmodulin, and guanylate cyclase activity, and plasma catecholamines in rats. 289 92

Nicardipine was found to produce a concentration-dependent depression of the isometric contraction of the isolated, spontaneously beating atria of the guinea-pig. It also depressed the atrial rate of the isolated, spontaneously beating atria of the guinea-pig. The effect of the increasing concentrations of nicardipine on the heart rate was negligibly weaker than its effect on the isometric contraction. A time-dependent depression of the isometric contraction and the atrial rate after the addition of a single dose of nicardipine was also found up to the 10th min. Calcium almost completely, isoprenaline completely and aminophylline partially antagonized the depressive action of nicardipine on the isometric contractility of the atria. Only isoprenaline antagonized the negative chronotropic action of higher doses of nicardipine. It is possible that these substances restore the contractility by compensating the calcium balance, previously changed by nicardipine, or by producing an increase in the intracellular cAMP content (isoprenaline and aminophylline).
 ...
PMID:[Effects of nicardipine on the spontaneous beat of isolated atria of guinea pigs]. 296 60

Previous studies on the regulation of responses of neutrophils to fMet-Leu-Phe have demonstrated the relevance of the role of the rate of occupation of the receptors by the stimulant. When this rate is decreased by presenting the peptide to neutrophils over a period of time by means of an infusion pump, the activation of the respiratory burst and of the secretion is greatly depressed or is absent. This paper deals with further investigations on the mechanisms of this desensitization, which previous results have shown to consist of an uncoupling between the ligand-receptor complexes and the target for cell responses, caused by the deceleration of the initial rate of occupation of the receptors. The data presented here demonstrate that this desensitization is not linked to the formation of a negative intermediate such as cAMP, but is associated with: (i) a depression of the rate and magnitude of the phosphatidylinositol response (activation of phosphatidylinositol turnover measured as modification of incorporation of [32P]Pi and [3H]glycerol into phosphatidylinositol and phosphatidic acid); (ii) a deceleration of the rate of the release of bound Ca2+, without a decrease in the total quantity of Ca2+ liberated (measured as fluorescence changes of chlorotetracycline treated neutrophils); (iii) a slower rise of cytosolic free Ca2+ concentration [Ca2+]i, without a decrease in the magnitude of the final increase of [Ca2+]i (monitored with Quin 2). These findings, which are discussed in relation to the recent hypotheses on the transduction reactions of receptor-mediated stimuli for neutrophil responses, are consistent with a mechanism of desensitization involving decreased production of diacylglycerol by the hydrolysis of phosphatidylinositol and deficient activation of Ca2+-phospholipid-dependent protein kinase C.
 ...
PMID:Mechanism of desensitization of neutrophil response to N-formylmethionylleucylphenylalanine by slow rate of receptor occupancy. Studies on changes in Ca2+ concentration and phosphatidylinositol turnover. 298 66

This study evaluated the effect of prostaglandin I2 (PGI2) on fibronectin-mediated macrophage phagocytosis in vivo and in vitro. Phagocytosis measured in vivo in rats by the vascular clearance rate and hepatic localization gelatinized sheep erythrocytes was inhibited in a dose-dependent manner after intravenous administration of PGI2. Phagocytosis was assessed in vitro in terms of uptake of fibronectin-dependent gelatinized sheep erythrocytes by monolayers of casein-elicited rat peritoneal macrophages. Concentrations of 1 ng/ml PGI2 or greater resulted in inhibition of particle internalization but not attachment to macrophages. This inhibitory effect was enhanced by aminophylline, a phosphodiesterase inhibitor. PGI2 increased cAMP levels and these were further increased in the presence of aminophylline. These data indicate that PGI2 inhibits macrophage uptake of gelatinized particles and support the idea that this is mediated by increased intracellular levels of cyclic AMP. PGI2 should thus be considered a potential etiologic factor in the phagocytic depression observed in association with thrombosis.
 ...
PMID:Influence of prostaglandin I2 on fibronectin-mediated phagocytosis in vivo and in vitro. 298 44

We have investigated the type of purine receptor in the guinea-pig olfactory cortex, using pial surfaces slices maintained in vitro. Adenosine (0.1 to 100 mumol/l) bath applied in the presence of the uptake inhibitor nitrobenzylthioinosine, depressed the evoked potentials in a dose related fashion. Synthetic and uptake resistant adenosine analogues had the same effect as adenosine and the order of potency of these was: 5'-N-ethylcarboxamide adenosine greater than L-N6-phenylisopropyl adenosine (L-PIA) = N6-cyclohexyladenosine = 2-chloroadenosine greater than adenosine greater than D-N6-phenylisopropyladenosine (D-PIA). The D-stereoisomer of PIA was 45 times less potent than L-PIA. The methylxanthine compounds 8-phenyltheophylline (3 mumol/l) and 3-isobutyl-1-methylxanthine (50 mumol/l) antagonised the depression produced by L-PIA. Rolipram, a phosphodiesterase inhibitor, in concentrations up to 100 mumol/l had no effect on the evoked potentials or on adenosine action. Forskolin, a cAMP stimulant, slightly increased the amplitude of the evoked potential, and partly reversed the depressant effect of adenosine. Noradrenaline had no effect either alone or in the presence of adenosine. The results of these experiments indicate the existence of A1 subtype adenosine receptors in the guinea pig olfactory cortex probably linked to a depression of intracellular cAMP.
 ...
PMID:Adenosine-induced depression of synaptic transmission in the isolated olfactory cortex: receptor identification. 298 40

Microiontophoretic injection of cAMP (but not of non-cyclic AMP) into Helix snail neurons induces rapid reversible membrane depolarization. The reversa potential of the cAMP response varies between +10 and -30 mV in different cells. The amplitude of the responses gradually increases (15 experiments), decreases (4 experiments) or remains unchanged (40 experiments) when the interval between the injections is less than 5 minutes. The identified neurons of the different preparations exhibit different types of dynamic changes in the amplitude of the responses to repeated cAMP injections. The possible role of the retaining current in the origin of the potentiation of cAMP responses was investigated. Potentiation of cAMP responses was preserved after the retaining current was switched off only in cases with no membrane depolarization due to spontaneous leakage of the substance from the microelectrode. It is suggested that potentiation or depression of cell responses to repeated cAMP injections is caused by dynamic changes in the cell cAMP system.
 ...
PMID:[Dynamic changes in the response of molluscan neurons to cyclic AMP with repeated injections]. 298 47

Cellular ATP levels were measured with the luceferin-luciferase enzyme method in incubated preovulatory granulosa cells in vitro from PMSG-treated immature rats. The ATP levels were depressed by both FSH and LH, FSH being the more effective. Adenosine enhanced the ATP levels about 3-fold, but the depressive effects of gonadotropins could not be overcome by the addition of adenosine. Uptake of adenosine in granulosa cells followed Michaelis-Menten kinetics, with a Km of 15.9 +/- 3.6 microM and a maximum velocity of 1.6 +/- 0.1 pmol/min X 10(5) cells. The half-time for uptake of adenosine was about 40 min. The maximal uptake of adenosine was lowered from 48 +/- 5 to 30 +/- 1 pmol/10(5) cells by FSH treatment of the cells. The basal secretions of cAMP and progesterone from the granulosa cells were slightly but significantly enhanced by adenosine alone. Adenosine markedly enhanced FSH-stimulated cAMP secretion, but not progesterone secretion. A nonmetabolizable adenosine analog, 2-chloro-adenosine, did not affect the ATP levels or the secretion of cAMP from granulosa cells. This study confirms previous observations that adenosine can increase ATP levels and amplify the response to gonadotropins in gonadal cells. A novel finding is that the levels of ATP in granulosa cells are markedly depressed by gonadotropins. It is speculated that this depression of ATP may be a factor in the metabolic control of granulosa cells.
 ...
PMID:Gonadotropin depression of adenosine triphosphate levels and interaction with adenosine in rat granulosa cells. 300 59

Exposure of FRTL-5 cells to iodide (I-) in excess of 3 microM suppresses the concentrative uptake of I-. The depression of I- uptake measured at the steady state is due to decrease in the rate of I- influx and not to an effect on I- efflux. Exposure to NaI is associated with decreased T4 secretion and also depressed Na+-dependent amino acid accumulation. The depression in I- and amino acid transports increases proportionately with the duration of exposure and concentration of I- used but is not associated with alterations in FRTL-5 cell cAMP levels. The I- suppression effect is blocked, however, when methimazole is present during the incubation with NaI. In agreement with studies in vivo, I- suppression in FRTL-5 cells appears to depend on an intermediate in the organification process and to be independent of a TSH-induced cAMP-mediated action.
 ...
PMID:Iodine suppression of iodide uptake in FRTL-5 thyroid cells. 300 60


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>