Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:4.6.1.1 (adenylate cyclase)
19,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fat cells were preincubated for 2 h in the presence and absence of growth hormone (GH) and Dexamethasone (Dex) before the addition of increasing concentrations of either epinephrine, theophylline or glucagon and final incubation of the cells for an additional 5 minutes. GH and Dex increased by 85%, 28% and 72%, respectively, the cAMP levels reached in the sole presence of 10(-5)M epinephrine, 10(-2)M theophylline or 5 X 10(-5)M glucagon. An adenylate cyclase particulate preparation shows that epinephrine decreases Km from 2mM to 0.6 MM and increases Vmax and the strength of interaction value (n) from 0.91 to 1.75.
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PMID:Hormonal control of fat cells adenylate cyclase. 18 30

The influence of steroid hormones on the response of human astrocytoma cells (1321N1) to prostaglandin E(1) (PGE(1)) has been investigated. Responsiveness to PGE(1) was determined by measuring the conversion of [(3)H]ATP to cyclic [(3)H]AMP in cells prelabeled with [(3)H]adenine. After incubation of the cells with dexamethasone, a marked increase in both the maximal effect (2- to 3-fold) and the potency (5-fold) of PGE(1) was observed. The effect was specific for the action of PGE(1) in that no change in the response of the cells to isoproterenol was observed. The EC(50) for dexamethasone was 0.001 muM and the effect was dependent on the presence of serum. The effect of dexamethasone was first observed after a 30- to 60-min lag and was maximal by 6-8 hr. Preconfluent cultures (3 days after seeding) exhibited optimal responsiveness to glucocorticoids. Both hydrocortisone and corticosterone mimicked the effect of dexamethasone but both were less potent. The action of dexamethasone was blocked by progesterone, testosterone, and 17alpha-methyltestosterone. Cycloheximide, at a concentration (1.0 mug/ml) that blocked protein synthesis (>90%) in 1321N1 cells, totally prevented the effect of dexamethasone on the response of the cells to PGE(1). Upon removal of dexamethasone from cells treated for 16 hr, responsiveness to PGE(1) returned to control levels with a half-time of 4 hr. Dexamethasone also was found to increase the response to PGE(1) of a Rous sarcoma virus-transformed human astrocytoma cell line and the WI-38 human fibroblast line. The most obvious interpretation of our findings is that glucocorticoids induce the synthesis of a protein that selectively modifies the sensitivity of adenylate cyclase to PGE(1).
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PMID:Glucocorticoids increase the responsiveness of cells in culture to prostaglandin E1. 20 Sep 33

We have previously shown that bone cells possess glucocorticoid receptors and that, in addition to being inhibitory to cell growth, glucocorticoid treatment potentiates the ability of parathyroid hormone (PTH) to stimulate cyclic AMP (cAMP) formation. This study extends those observations to specific subpopulations of bone cells and explores the mechanism of the cAMP augmentation. Subpopulations of cultured bone cells derived from 20-d-old fetal rat calvaria were enriched for "osteoblast-like" (OB) and "osteoclast-like" (OC) cells by sequential collagenase digestion. OC cells released during the first 30 min of collagenase digestion were characterized by low alkaline phosphatase activity, a cAMP response to salmon calcitonin (CT), but only a small cAMP response to bovine PTH. In contrast, OB cells released between 30 and 120 min of collagenase digestion, possessed high alkaline phosphatase activity, responded with a large cAMP rise to PTH, but exhibited no response to CT. Glucocorticoid receptors, with similar properties, were demonstrated in both populations (K(d) congruent with 5 nM, N(maximum) congruent with 400 fmol/mg cytosol protein). Dexamethasone equivalently inhibited cell growth and alkaline phosphatase activity in both populations. Dexamethasone potentiation of cAMP generation occurred after PTH but not CT stimulation. A greater enhancement of cAMP generation observed in OB cells appears to result from two glucocorticoid actions: (a) stimulation of adenylate cyclase and (b) inhibition of phosphodiesterase. Only the latter mechanism was found in OC cells. Dexamethasone-treated cells showed an increase in both sensitivity and maximal response of cAMP to PTH. The possible relationship of these actions to the mechanism of glucocorticoid-induced osteopenia is discussed.
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PMID:Glucocorticoid receptors and actions in subpopulations of cultured rat bone cells. Mechanism of dexamethasone potentiation of parathyroid hormone-stimulated cyclic AMP production. 22 Feb 82

We studied the effects of administration of dexamethasone, 2 mg orally every 6 hr for 4 doses, on circulating thyroid hormone levels in hyperthyroid Graves' disease patients and in normal subjects. Serum triiodothyronine (T3), thyroxine (T4) and thyroglobulin (Tg) fell significantly below baseline values within 24 to 48 h after the first dose of dexamethasone in hyperthyroid patients; the values returned to or toward baseline levels in the subsequent 5 to 6 days. Serum T3 fell transiently in normals but to a much smaller degree than in hyperthyroid patients; T4 and Tg showed no significant change. Dexamethasone had ni inhibitory effect on the thyroid response to exogenous TSH in the hyperthyroid patients. Studies in vitro demonstrated lack of any appreciable effect by dexamethasone or hydrocortisone on stimulation of human thyroid adenyl cyclase by TSH or immunoglobulin G(IgG) from patient with Graves' disease. The fall in serum T3 without a change in serum T4 in normals suggested an effect of dexamethasone on peripheral conversion of T4 to T3. However, the markedly greater, more persistent drop in T3 in the hyperthyroid patients, as well as the associated drop in T4 and Tg, suggested an additional effect of dexamethasone administration on thyroid secretion in these patients. Preservation of thyroidal response to TSH during dexamethasone administration both in vivo and in vitro indicated that dexamethasone had not impaired thyroidal cellular processes per se. The data were consistent with an effect of dexamethasone on thyroid stimulator. The putative stimulator does not appear to be normal pituitary thyrotropin (TSH), since TSH was not detected in serum of anyof the patients studied. Additionally, the changes observed were too rapid to be explained by a steroid-induced fall in the level of a circulating IgG thyroid stimulator. The data are consistent with the possibility that there may be a non-TSH non-IgG thyroid stimulator in Graves' disease.
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PMID:Acute effects of corticosteroids on thyroid activity in Graves' disease. 117 32

Prolonged exposure to hypoxia, as at high altitude, results in increased vascular permeability that may be ameliorated by administration of glucocorticoids. To understand mechanisms underlying these observations, cultured bovine aortic and pulmonary artery endothelial cells (ECs) were subjected to hypoxia, and changes in monolayer permeability and adenosine 3',5'-cyclic monophosphate (cAMP) levels were assessed. Exposure of both types of cultured ECs to hypoxia (PO2 approximately 14 Torr) led to a time- and dose-dependent increase in monolayer permeability, as measured by diffusion of radiolabeled solutes, which was associated with a progressive decrease in EC cAMP levels from 60 to 15 pmol/mg protein, and a decrease in EC adenylate cyclase activity. The change in endothelial barrier function was prevented by addition of cAMP analogues. Pertussis toxin protected EC monolayers from hypoxia-mediated increase in permeability while maintaining cAMP levels and adenylate cyclase activity. Addition of dexamethasone to EC monolayers before or simultaneously with their incubation under hypoxic conditions blocked the hypoxia-mediated increase in monolayer permeability. Dexamethasone pretreatment also prevented the decline in cAMP and adenylate cyclase levels in oxygen-deprived cultures. These data indicate that hypoxia decreases EC barrier function by lowering adenylate cyclase activity and cellular cAMP levels. They suggest that dexamethasone may exert its protective effect, in part, by preventing the hypoxia-induced decline in adenylate cyclase activity, leading to an increase in cellular cAMP and maintenance of EC barrier function.
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PMID:Hypoxia-induced increased permeability of endothelial monolayers occurs through lowering of cellular cAMP levels. 131 75

Adrenergic stimulation and glucocorticoids have been hypothesized to control the development of beta-adrenergic receptors and responsiveness. In the current study, rats were exposed to a beta-agonist (terbutaline) or a glucocorticoid (dexamethasone) during late gestation, and the development of adenylate cyclase activity and beta-receptor binding was evaluated in membranes prepared from the heart and liver. In control heart, basal, isoproterenol-stimulated and forskolin-stimulated adenylate cyclase showed distinct developmental spikes of activity that were unrelated to changes in receptor binding sites, but that instead corresponded temporally to periods of sympathetic neuronal activation. Prenatal exposure to terbutaline initially enhanced all three enzymatic measures in the immediate postpartum period but delayed the appearance and exaggerated the magnitude of the subsequent peaks; again, these changes occurred without specific relation to effects on receptor binding. Dexamethasone produced a similar shift in the peaks of cardiac enzyme activity. In the liver, where beta-adrenergic receptors and responsiveness decline after birth, terbutaline and dexamethasone had much smaller effects on adenylate cyclase. These results suggest that beta-adrenergic stimulation serves as a trophic factor controlling the ontogenetic rise of adenylate cyclase activity; regulation involves the level of the enzyme itself rather than changes in receptor binding capabilities or receptor-specific linkages. Consequently, prenatal administration of beta-agonists or glucocorticoids can cause long-term alterations in enzyme activity and responsiveness.
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PMID:Control of adenylate cyclase activity in developing rat heart and liver: effects of prenatal exposure to terbutaline or dexamethasone. 165 19

The present studies were undertaken to precise the mechanism through which glucocorticoids enhance the responsiveness of ovine adrenocortical cells to ACTH. Experiments using intact cells and crude adrenal membranes have shown that, at the level of the adenylate cyclase system, dexamethasone increases the number of ACTH receptors without modification of the catalytic subunit or of the GTP binding regulatory components Gs and Gi. Cells cultured with dexamethasone secreted more pregnenolone and more corticosteroids in response to 8-BrcAMP than did control cells. By contrast, dexamethasone did not increase corticosterone secretion by cells incubated in the presence of 22-(R)-hydroxycholesterol or of exogenous pregnenolone. Dexamethasone neither affected the incorporation of [14C] acetate into cellular cholesterol nor the amount of cholesterol present in mitochondria of unstimulated cells. However, dexamethasone-treated cells incubated in the presence of both 8-BrcAMP and aminoglutethimide exhibited higher amounts of mitochondrial cholesterol than control cells. These data indicate that dexamethasone enhances the number of cellular ACTH receptors together with increasing the cAMP-induced translocation of cholesterol from the cytoplasm into mitochondria and/or mitochondrial storage of cholesterol.
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PMID:Mechanism of glucocorticoid enhancement of the responsiveness of ovine adrenocortical cells to adrenocorticotropin. 215 73

The regulation of fibronectin (FN) biosynthesis by dexamethasone (a synthetic glucocorticoid), forskolin (an activator of adenylate cyclase), and transforming growth factor beta (TGF-beta) was examined in six human cell lines. Dexamethasone treatment produced the largest increase in FN biosynthesis in the fibrosarcoma cell line, HT-1080 (approximately 45-fold). This seems to result from a dexamethasone-mediated increase in FN mRNA stability which increases the message half-life from approximately 11 to 26 h. The relative instability of FN mRNA in the fibrosarcoma (t1/2 11 h) compared to normal fibroblasts (70 h) appears to result from the particular transformed phenotype of the HT-1080 cells. Forskolin and TGF-beta increase the rate of FN gene transcription in most of the cell lines. These effects (four- to six-fold) occur rapidly and do not require protein synthesis in the responsive cell lines which include normal fibroblasts. However, in the fibrosarcoma (HT-1080), a surprisingly large induction (20-30-fold) is observed and this induction is different from that in the normal fibroblasts and the other cell lines in that both protein synthesis and a lag period are required. Synergism is seen with dexamethasone and either forskolin or TGF-beta in HT-1080 cells increasing the rate of FN biosynthesis approximately 200-fold to a level similar to normal fibroblasts. This seems to result from a combination of FN mRNA stabilization (dexamethasone) and increased transcription (forskolin and TGF-beta).
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PMID:Regulation of fibronectin biosynthesis by dexamethasone, transforming growth factor beta, and cAMP in human cell lines. 245 32

Steroid hormones modulate the ability of cells to respond to hormones that act via cyclic AMP. In adipocytes of adrenalectomized rats, cyclic AMP accumulation and lipolysis in response to adrenaline are attenuated. However, the mechanism(s) of these effects are poorly understood. The effects of altered glucocorticoid status in vivo on the steady-state amounts of components of the hormone-sensitive adenylate cyclase were analysed in rat adipocytes. beta-Adrenergic receptors were analysed by using radioligand binding and immunoblotting with an anti-receptor antiserum. Neither the amount of radioligand binding nor the amount of beta-adrenergic-receptor peptide (Mr 67,000) was altered by adrenalectomy, whereas treatment of adrenalectomized rats with dexamethasone was found to increase both parameters by more than 25% with respect to the control. Forskolin-stimulated adenylated cyclase activity was unchanged in membranes isolated from adipocytes of adrenalectomized rats, but was decreased (50%) in those from dexamethasone-treated rats. The alpha-subunit of Gs was probed by using cholera-toxin-catalysed ADP-ribosylation. Immunoblotting was used to analyse the steady-state amounts of G-protein beta-subunits (beta-G35/36). Adrenalectomy was associated with decreases in the steady-state amounts of alpha-Gs (30%) and beta-G35/36 (50%). Dexamethasone treatment of adrenalectomized animals partially restored the lipolytic response of adipocytes to adrenaline and the amounts of alpha-Gs, increased the amounts of beta-G35/36 subunits from 50% to 150% of control values, increased beta-adrenergic receptors by more than 25% and decreased adenylate cyclase activity (50%). These results suggest that the steady-state amounts of components of hormone-sensitive adenylate cyclase are differentially regulated by glucocorticoids.
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PMID:Adipocyte G-proteins and adenylate cyclase. Effects of adrenalectomy. 253 94

Cultured peritubular cells prepared from the testes of 20-day-old rats contained both preproenkephalin (A) mRNA (1.5 kb) and amyloid beta-protein precursor mRNA (3.6 and 2.8 kb). The phorbol ester TPA and forskolin (an adenylate cyclase activator) increased the preproenkephalin mRNA abundance to 9.0 and 5.8 times the control, respectively. TPA alone had no effect on the intracellular cAMP level. A combination of TPA and forskolin elicited a synergistic increase in the ppEnk mRNA abundance over 30-fold. Dexamethasone potentiated the effect of forskolin but not of TPA. These results suggest that TPA regulates the preproenkephalin mRNA abundance through a cAMP-independent pathway. In contrast, TPA, forskolin, and dexamethasone showed little or no effect on the abundance of amyloid beta-protein precursor mRNA.
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PMID:Phorbol ester regulates the abundance of enkephalin precursor mRNA but not of amyloid beta-protein precursor mRNA in rat testicular peritubular cells. 254 64


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