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)

The effect of vanadate on the adenylate cyclase activity of rat cerebral cortex homogenates is described. In the absence of ethyleneglycol-bis-(beta-aminoethyl ether) N,N'-tetraacetic acid (EGTA), 10(-6)M vanadate inhibited enzyme activity by 23%, while 10 (-4) M and 10(-3) M stimulated the enzyme by 14 and 90%, respectively. In the presence of 0.2 mM EGTA, 10 (-6) M to 10(-3) M vanadate had only stimulating effects (18-450%). Additive effects of vanadate and noradrenaline on adenylate cyclase activity suggest different sites of action of these agents. Interaction of vanadate with both fluoride and guanyl-5'-yl imidodiphosphate had an apparently competitive character. Adenylate cyclase maximally stimulated by fluoride (10 mM) was inhibited by vanadate. This inhibitory effect was more pronounced in the absence of EGTA. Adenylate cyclase in the homogenates from the rat cerebral cortex in vivo invaded by spreading depression was slightly increased (up to 38%). This effect was abolished by low (10 (-7) M) vanadate. The results suggest that brain adenylate cyclase is stimulated by vanadate via the guanine nucleotide regulatory protein. The mechanism of vanadate's action, its modulation by calcium ions and the possible physiological role of these effects are discussed.
 ...
PMID:Vanadate and brain adenylate cyclase. Effect of spreading depression. 655 51

Heart sarcolemma from different animals was isolated for studying the effect of NaF on membrane-bound adenylate cyclase activity. Unlike dog and rabbit heart, a depression of adenylate cyclase by NaF was observed in sarcolemma from rat heart. There was a progressive attenuation of the NaF ability to stimulate the enzyme at different steps of the sarcolemmal isolation procedure. The activation by epinephrine in the presence of Gpp(NH)p also decreased progressively but unlike NaF, this agent did not show an inhibition of the enzyme. The inhibitory action of NaF was not reversed upon the treatment of heart membranes with deoxycholate or by Ca2+. Lubrol extract (supernatant) of a particulate fraction from rat heart, which showed NaF activation, returned the stimulatory response of the sarcolemmal adenylate cyclase to NaF. These results suggest that some regulatory factor is required for the stimulation of adenylate cyclase by NaF in myocardium and rat heart is susceptible for the loss of such a factor during the sarcolemmal isolation by the hypotonic shock-LiBr treatment method.
 ...
PMID:Association of adenylate cyclase inhibition by NaF with loss of a factor in rat heart sarcolemma. 662 5

We have hypothesized that the halothane-induced depression of myocardial contractility can be explained, at least in part, by halothane's depression of adenylate cyclase, previously demonstrated in whole homogenates of myocardial tissue. Canine myocardial sarcolemmal membranes, which contain the adenylate cyclase of myocardial cells, were separated from other cellular constituents. Halothane did not depress catecholamine-stimulated adenylate cyclase activity in this preparation. Reconstitution of the sarcolemmal membrane preparation with a 100,000 X g adenylate cyclase-free supernatant restored the depressant effect of halothane on adenylate cyclase stimulated by guanosine triphosphate (GTP) 100 microM alone (-55%, P less than 0.01) or in combination with l-isoproterenol 1 microM (-38%, P less than 0.05) or 2.5 microM (-40%, P less than 0.01). Dilution of the supernatant to half-strength decreased the magnitude of the halothane-induced depression of adenylate cyclase activity to 19% (P less than 0.01); at one-quarter dilution, the effect was no longer significant. This study demonstrates the presence of endogenous modulators of the action of halothane on canine myocardial adenylate cyclase that can be reversibly separated from the adenylate cyclase complex.
 ...
PMID:Halothane inhibition of canine myocardial adenylate cyclase--modulation by endogenous factors. 670 45

The effect of chronic experimental diabetes on the adenylate cyclase system (AC) in the rat heart was investigated. Rats were made diabetic by an intravenous injection of streptozotocin (65 mg/kg), hearts were removed 8 weeks later and washed cell particles were isolated. AC activity was measured in the absence and presence of different concentrations of forskolin, NaF, GTP analogue [Gpp(NH)p] or epinephrine. A significant depression in the epinephrine stimulated AC activity was observed in diabetic hearts. Basal AC activity and stimulation of AC with forskolin, NaF and Gpp(NH)p were not significantly different between control and diabetic preparations. These results indicate no apparent alterations in the regulatory or catalytic properties of AC in hearts from chronic diabetic rats. The observed depression in epinephrine stimulated AC activity may account for the depressed inotropic action of catecholamines in the diabetic cardiomyopathy.
 ...
PMID:Alterations in adenylate cyclase activity due to streptozotocin-induced diabetic cardiomyopathy. 670 25

The Warburg method was used to study the action of adenosine on several phases of rat cerebral cortex metabolism, using cortex slices or homogenates. In the presence of exogenous glucose in vitro, oxygen consumption and lactate production are not affected by adenosine in sections. In vivo, there is an increase of oxygen consumption and of lactate production but which are not significant. Adenosine may activate metabolic pathways, since the observed metabolic changes remain constant during the period of activity of adenosine (30 to 60 min) and disappear concomitantly with adenosine. The action of adenosine is much more evident in sections from the brains of injected animals, where the increase of lactate production becomes significant. This suggests that in this case adenosine favors a better utilization of glycogen via an activation of adenylate cyclase. The increased activity of G-6-PDH was observed in vitro but was not significant in vivo. These observations were confirmed with homogenates from the in vivo series by the significant decrease of inorganic phosphate levels, consistent with an increased formation of nucleotide phosphates. The increased cerebral glucose concentration is perhaps a result of increased blood glucose levels, in turn resulting from the known depression of insulin release by adenosine, or from a preferential utilization of glycogen, resulting from the activation of adenylate cyclase.
 ...
PMID:Action of adenosine on energy metabolism and on glucose-6-phosphate dehydrogenase in rat brains. 672 44

The glucagon-stimulated (coupled) activity of rat liver plasma-membrane adenylate cyclase could be selectively modulated by the anionic drug phenobarbital, whereas the fluoride-stimulated (uncoupled) activity remained unaffected. It is suggested that the cationic drug phenobarbital preferentially interacts with the external half of the bilayer, as the negatively charged phospholipids are found at the cytosol-facing side. This results in a selective fluidization of the external half of the bilayer, leading to a depression in the high-temperature onset of the lipid phase transition (from 28 degree to 16 degree C) occurring there. This was detected both by e.s.r. analysis, using a fatty acid spin probe, and also by Arrhenius plots of glucagon-stimulated activity, where the enzyme forms a transmembrane complex with the receptor and is sensitive to the lipid environment of both halves of the bilayer. However, in the absence of hormone, adenylate cyclase only senses the lipid environment of the inner (cytosol) half of the bilayer. Thus its fluoride stimulated activity and Arrhenius plots of this activity remained unaffected by the presence of phenobarbital (less than 12 mM) in the assay. These results support the view that independent modulation of the fluidity or chemical constituents of each half of the bilayer can selectively affect the receptor-coupled and uncoupled activities of adenylate cyclase.
 ...
PMID:Phenobarbital selectively modulates the glucagon-stimulated activity of adenylate cyclase by depressing the lipid phase separation occurring in the outer half of the bilayer of liver plasma membranes. 732 77

A series of six experiments was conducted to investigate the effects of Mg deficiency in the young rat on parathyroid hormone (PTH) activity and on response to parathyroid extract (PTE) and to endogenously produced PTH stimulated by dietary Ca deficiency. Major criteria employed were 45Ca release from pre-labeled bone and urinary excretion of cAMP. Mg deficiency was accompanied by lowered 45Ca mobilization and urinary cAMP excretion, indicating either a depression in PTH secretion or tissue insensitivity to it. Administration of PTE resulted in equivalent increases in 45Ca mobilization irrespective of Mg status but increased cAMP excretion only in Mg-adequate animals, thus indicating a depressed sensitivity of kidney to PTH in the Mg-deficient animal. In vitro response of kidney cortex from Mg-deficient animals to PTE added to incubation medium indicated no defect in the adenyl cyclase system. Endogenous stimulation of PTH by low Ca diet increased cAMP in Mg-adequate animals but not in rats with pre-existing Mg deficiency. Mg deficiency did not reduce cAMP previously stimulated by Ca deficiency.
 ...
PMID:Effect of magnesium deficiency on rat bone and kidney sensitivity to parathyroid hormone. 740 Aug 50

Previous studies by this laboratory showed that the pesticide lindane rapidly and potently inhibits gap junctional communication in myometrial smooth muscle cells. This study examined the possible role of cAMP or arachidonic acid in lindane's elimination of myometrial gap junctional communication. Lindane produced concentration-dependent increases in cAMP of 1.21, 2.94, 6.06, and 8.69 pmol/mg protein with 0.1, 1, 30, and 100 microM lindane, respectively, compared to solvent-treated controls (1.27 pmol/mg protein). Lindane also increased release of tritiated arachidonic acid to 342, 509, 852, 1236, 1639, and 4454 dpm/micrograms protein with 0.01, 0.1, 1, 10, and 100 microM lindane, respectively, compared to solvent controls (342 dpm/micrograms protein). Transfer of Lucifer Yellow dye was used as a measure of gap junctional communication. Both 8-br-cAMP (98, 97, 54, and 4% transfer seen with 0, 1, 10, and 100 microM cAMP) and arachidonic acid (98, 73, 54, 31, and 0% dye transfer for 0.1, 1, 10, 100, and 1000 nM arachidonic acid) depressed dye transfer in cultured myocytes. Although the adenylate cyclase inhibitor 2',3'-dideoxyadenosine completely reversed forskolin-induced depression of dye transfer (1 microM forskolin, 22% transfer), it had no effect with lindane, indicating that lindane's depression of dye transfer was independent of adenylate cyclase activation. Lindane's inhibition of dye transfer was effectively reversed by growing myometrial cells under arachidonic acid-free conditions in the presence of eicosapentaenoic acid, a fatty acid that competes with arachidonic acid for the sn-1,2 position of membrane phospholipids: 0, 15, 40, and 88% dye transfer occurred in the presence of 0.01, 0.1, 1, and 10 microM eicosapentaenoic acid with 30 microM lindane. This implies that arachidonic acid release may be a critical event associated with lindane's inhibition of gap junctional communication in uterine myocytes.
 ...
PMID:Lindane-induced elimination of gap junctional communication in rat uterine myocytes is mediated by an arachidonic acid-sensitive cAMP-independent mechanism. 748 32

Addition of glucose to cells of the yeast Saccharomyces cerevisiae growing on a nonfermentable carbon source triggers a rapid, transient increase in the cAMP level. The occurrence of this cAMP spike appears to be correlated inversely with the glucose-repression state of the cells. This was also observed for the hex2 mutant, which is deficient in glucose repression and which displayed the cAMP signal constitutively. When cells of the hex2 mutant were starved for nitrogen on a glucose-containing medium, they rapidly lost viability, similarly to mutants with overactivation of the Ras-adenylate cyclase pathway. Flow cytometry measurements showed that G1 arrest of the hex2 mutant under such conditions was incomplete. Trehalose accumulation, a typical feature of cells entering the stationary phase G0, was very short-lived in the hex2 mutant under the same conditions. These results are in agreement with the presence of continuous glucose-triggered activation of cAMP synthesis in hex2 cells on a glucose-containing nitrogen-starvation medium. In the course of these experiments a spontaneous suppressor mutant, shx (for suppressor of hex2), was isolated which survived nitrogen starvation on a glucose-containing medium much better than the hex2 strain. It also showed normal G1 arrest and much longer accumulation of trehalose. The suppressor mutation also caused inability to grow on nonfermentable carbon sources and absence of invertase depression, and it was epistatic to hex2 for these characteristics also. The isolation of this epistatic depression mutation supports the idea that the defect in glucose repression of the hex2 mutant is the cause of its rapid loss of viability during nitrogen starvation on a glucose-containing medium.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Constitutive glucose-induced activation of the Ras-cAMP pathway and aberrant stationary-phase entry on a glucose-containing medium in the Saccharomyces cerevisiae glucose-repression mutant hex2. 755 Oct 24

The aim of the present study was to determine whether two classical macrophage activators, bacterial lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma) could affect the accumulation of the second messenger cAMP in cultured rat microglia and astrocytes. Purified microglia and astrocyte secondary cultures obtained from the neonatal rat were grown for 3 days in basal medium Eagle (BME) + 10% fetal calf serum (FCS). Exposure of microglia to LPS resulted into a dose- and time-dependent decrease in the accumulation of cAMP induced by receptor-mediated (isoproterenol or prostaglandin E2) or direct (forskolin) activation of adenylate cyclase. The inhibitory effect of LPS was rapid (a 10 min preincubation was sufficient to approach a maximal effect), occurred at low doses (IC50 = 1.2 ng/ml), and was not abrogated by pertussis toxin. A selective inhibitor of type IV phosphodiesterase (rolipram, 100 nM) prevented the effect of LPS on cAMP accumulation, while inhibitors of other forms of phosphodiesterase were unable to do so. IFN-gamma (100 u/ml) also caused a depression of the evoked cAMP accumulation in microglia after a 10 min preincubation, and its effect was prevented by rolipram, as in the case of LPS. Astrocytes differed from microglia in that LPS (1-100 ng/ml) did not inhibit the accumulation of cAMP induced by either isoproterenol or forskolin; on the other hand, IFN-gamma did have an inhibitory effect (though less pronounced than in microglia) that could be prevented by rolipram.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Interferon-gamma and lipopolysaccharide reduce cAMP responses in cultured glial cells: reversal by a type IV phosphodiesterase inhibitor. 755 45


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