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)

A model has been presented for the role of the kidney in the physiologic and pathophysiologic control of erythropoiesis. It is postulated that an oxygen deficit created by anemia or hypobaric hypoxia results in the release of prostacyclin and its metabolite 6-keto PGE1, and the release of PGE2 with ischemic hypoxia. Prostacyclin, 6-keto-PGE1, or PGE2 activation of adenylate cyclase, an increase in cyclic AMP, activation of a protein kinase and the phosphorylation of hydrolases, which have been released from lysosomes by hypoxia, lead to increased biosynthesis of erythropoietin (Ep). The mechanism of labilization of lysosomes and the release of hydrolases from these cell organelles is postulated to be related to increases in cyclic GMP levels in a renal cell. An Ep-producing human renal carcinoma cell line grown in tissue culture has been demonstrated to produce significant amounts of PGE2. Meclofenamate, an inhibitor of prostaglandins synthesis, was found to inhibit in vitro production of PGE2, Ep, and dome formation in these renal carcinoma cells, giving support to our hypothesis that pathophysiologic production of Ep tumor cells depends upon prostaglandins production. An Ep-producing clone from this renal carcinoma cell line has been developed that contains low electron density (LED) cells after the cells reach confluency, which show a cytoplasm, with abundant and widely dilated endoplasmic reticulum, an oval nucleus, dispersed chromatin, and prominent nucleoli. These are the cells responsible for dome formation and Ep production. Non-EP-producing clones have also been produced from this renal carcinoma cell line, which did not produce domes even at high cell density and had a distinctly different cell type than the Ep-producing clone. Thus, it is postulated that prostacyclin (PGI2) and its metabolite 6-keto PGE1 play a significant role in hypoxic hypoxia stimulation of Ep production and PGE2 is involved in ischemic hypoxia and renal carcinoma cell production of Ep. A modulating effect of PGE2 and PGD2, the two primary bone marrow prostaglandins, has been proposed in Ep stimulation of the erythroid progenitor cell compartment (CFU-E and BFU-E).
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PMID:Effects of prostaglandins on erythropoiesis. 654 52

The ultrastructural localization of adenylate cyclase activity has been investigated in unfixed guinea-pig peritoneal macrophages in different physiological states (such as suspension, adhesion and phagocytosis) using a medium containing 5'-adenylyl-imidodiphosphate (AMP-PNP) as the substrate. Adenylate cyclase activity was observed in cytoplasmic vacuoles of macrophages in suspension; in the perinuclear space, endoplasmic reticulum, Golgi complex and pseudopods of adherent macrophages; and surrounding phagocytosed polystyrene particles. The activity was inhibited by Alloxan added to the incubation medium and no staining was observed when AMP-PNP was omitted from the medium. The segregation of this enzyme to phagocytic vacuoles and pseudopods may have significant implications in understanding cyclic nucleotide function in adhesion and phagocytosis.
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PMID:Differences of adenylate cyclase localization in guinea-pig peritoneal macrophages under different physiological conditions: an ultracytochemical study. 662 54

Methods are described for the analysis and purification of the blood-sinusoidal domains of rat liver plasma membranes using a combination of sucrose and Ficoll density gradient centrifugation. Use has been made of 125I-labelled wheat-germ agglutinin and hormone-stimulated adenylate cyclase to identify the blood sinusoidal fraction, which may be resolved from Golgi and endoplasmic reticulum markers on Ficoll gradients.
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PMID:Analysis and purification of the blood-sinusoidal domain of rat liver plasma membrane. 687 Nov 87

Hepatocytes, endothelial and Kupffer cells were isolated from young adult (3 month) and old (24 month) rat livers and the activities of some plasma membrane, endoplasmic reticulum, mitochondrial, lysosomal and soluble enzymes compared using biochemical and electron microscope cytochemical techniques. Age-associated changes included: a decrease in glucose-6-phosphatase activity both in hepatocytes and sinus lining cells; and increase in alkaline phosphatase in endothelial cells but a decrease in hepatocytes; reduced basal and glucagon-induced adenyl cyclase in hepatocytes and endothelial cells and an increase in the number of hepatocytes with gamma-glutamyl transferase reaction. Cytochemistry showed that heterogeneity may also be characteristic of senescence particularly with regard to hepatocyte glucose-6-phosphatase which was absent in some cells, low in many cells but high in some and gamma-glutamyl transferase which was normally lacking from hepatocytes but localised as large deposits of reaction product on the plasma membranes of occasional cells isolated from old donors.
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PMID:Effects of age on rat liver enzymes. A study using isolated hepatocytes, endothelial and Kupffer cells. 706 Sep 52

Electron cytochemistry was used to study the distribution of adenylate cyclase in the rat brain cortex and nucleus caudatus. In neurons and glial cells, the enzyme was localized on the outside surface of plasma membrane, within the perinuclear space, in the cisterns of endoplasmic reticulum and the Golgi apparatus. In capillaries, it was detected on the luminal surface of endothelial cells and along the basal layer. The addition of NaF and isoproterenol to the incubation medium led to the increased adenylate cyclase activity.
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PMID:[Electron cytochemical study of the cerebral adenylate cyclase of rats]. 729 93

Ultrastructural localization of adenylate cyclase (AC) activity was investigated in suspensions of unfixed isolated rat thymocytes using a medium containing 0.6 mM 5'-adenylylimidodiphosphate (AMP-PNP) as a substrate, 10 mM MgSO4 as an activator, 5 mM theophylline as an inhibitor of 3' 5'-AMP-phosphodiesterase and 2 mm lead nitrate as a capturing agent. AC activity was demonstrated in plasma membrane, perinuclear space, endoplasmic reticulum, Golgi complex, centriole microtubules and mitochondria. AC was activated with 10(-4) M adrenaline in the presence of 5'-guanylylimido-diphosphate (GMP-PNP) as well as with 10(-2) M NaF. In the cells incubated in a medium devoid of theophylline and containing 5'-AMP instead of AMP-PNP, 5'-nucleotidase activity was observed in the same cell structures as AC activity, Hydrolysis of 5'-AMP in the nucleus was much stronger than that of AMP-PNP. 10 mM NaF markedly inhibited hydrolysis of 5'-AMP in all cell structures. No staining was observed with 2 mM beta -glycerophosphate as a substrate. Incubation of unfixed thymocytes in media containing AMP-PNP, 5'-AMP or p-nitrophenyl phosphate, but not beta -glycerophosphate, induced both in the nucleus and in the cytoplasm in some cells an appearance of a transitory reticular formation consisting of about 303nm thick strands which could penetrate the nuclear envelope and plasma membrane and form connections with adjacent cells. The transitory reticular formation seems to belong to the cytoskeleton and to be involved in cell aggregation.
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PMID:Ultracytochemical localization of adenylate cyclase activity in rat thymocytes. 729 93

The mechanism of the potentiating effect of vasoactive intestinal peptide (VIP) on cholecystokinin (CCK-8)-induced amylase release was studied in isolated and perifused pancreatic acini of the guinea pig. VIP (30 pM-10 nM) potentiated CCK-8 (100 pM)-induced amylase release. Unexpectedly, VIP inhibited CCK-8-induced intracellular Ca2+ oscillations. Forskolin (10 microM), an activator of adenylate cyclase, potentiated CCK-8 (100 pM)-induced amylase release with a time course similar to that observed with VIP. Caffeine (20 mM) inhibited both amylase release and Ca2+ oscillations in response to CCK-8, suggesting that inhibition of Ca2+ oscillations does not necessarily lead to a potentiation of amylase release. When intracellular Ca2+ concentration ([Ca2+]c) was raised by thapsigargin (10 microM), a selective inhibitor of Ca(2+)-ATPase in the endoplasmic reticulum (ER), VIP (10 nM) induced significantly greater amylase release than that induced by VIP alone. When [Ca2+]c was lowered by preincubation with BAPTA-AM (25 microM), a cell-permeant Ca2+ chelator, VIP-induced amylase release was completely abolished. These results suggest that VIP, in spite of its inhibitory action on Ca2+ oscillations, facilitates a Ca(2+)-dependent process distal to the increase in [Ca2+]c to potentiate CCK-8-induced amylase release.
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PMID:Potentiation of cholecystokinin-induced amylase release by peptide VIP in guinea pig pancreatic acini. 756 61

Intracellular Ca2+ (Cai2+) stores contribute significantly to Ca2+ signaling in many types of cells. We studied the role of inositol trisphosphate (InsP3)-sensitive Ca2+ stores, a principal Cai2+ store that presumably is within the endoplasmic reticulum (ER), in cell signaling by examining the effect of thapsigargin (Tg), an ER Ca2+ pump inhibitor that depletes the ER Ca2+ pool, on ACTH secretion. Preincubation for 6-24 h with 2-20 nM Tg had no effect on the resting cytosolic free Ca2+ concentrations ([Cai2+]) but inhibited the ionomycin-stimulated spike-type increase in [Cai2+], which is mediated by InsP3-independent Cai2+ release from the ER, in a dose-dependent (IC50, 4 nM) and time-dependent manner. In ER Cai(2+)-depleted cells, the spike phase (initial 5 min) of the ACTH secretory response to arginine vasopressin (AVP), which is mediated by InsP3-induced Cai2+ release, was also attenuated (IC50, 7.3 nM). However, the spike phase of the ACTH secretory response to AVP was inhibited to a much greater degree than the spike-type response to ionomycin, suggesting that ER Cai2+ stores might have functions other than simply providing Ca2+ for InsP3-stimulated Cai2+ release. Tg pretreatment (IC50, 12 nM) also markedly inhibited the sustained plateau (final 15-min) phase of the ACTH secretory response to AVP, which is mediated by diacylglycerol-induced activation of protein kinase C and subsequent influx of extracellular Ca2+ via L-type voltage-sensitive Ca2+ channels (VSCC), but had no effect on the sustained (full 20 min) response to dioctanoylglycerol that directly activates protein kinase C. Tg had no effect on specific cell binding of [125I]AVP or on specific cell binding of [3H]phorbol 12,13-dibutyrate (except at 20 nM Tg), an index of protein kinase C concentration, or on protein kinase C activity. AVP significantly stimulated inositol trisphosphate accumulation, but pretreatment with Tg completely abolished this effect of AVP, whereas [3H]myoinositol incorporation into membrane-associated inositol lipids and inositol phosphates was unaffected. Thus, Tg-induced depletion of ER Cai2+ stores inhibited both the spike and plateau phases of the ACTH secretory response to AVP, presumably by inhibiting phospholipase C activity and the resulting generation of InsP3 and diacylglycerol. Preincubation with Tg inhibited, in a dose-dependent (IC50, 13 nM) and time-dependent manner, the sustained ACTH secretory response to corticotropin-releasing hormone (CRH) that is mediated by cAMP-induced activation of protein kinase A and Cae2+ influx via L-type VSCC, and the sustained response to forskolin, which directly activates adenylate cyclase.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Role of inositol trisphosphate-sensitive calcium stores in the regulation of adrenocorticotropin secretion by perifused rat anterior pituitary cells. 758 88

Cholera toxin (CT) consists of a pentameric B subunit which binds to ganglioside GM1 on the cell surface and an A subunit which activates adenylylcyclase. The latter process involves the reduction of A to the A1 peptide which ADP-ribosylates the stimulatory G protein, Gs of adenylylcyclase. There is a distinct lag phase between toxin binding and activation of adenylylcyclase. Little is known about the events during this lag including where A1 is generated and how it gains access to Gs on the cytoplasmic side of the plasma membrane. We explored the effects of several inhibitors of intracellular trafficking on the response of human SK-N-MC neurotumor and Caco-2 intestinal tumor cells to CT. Whereas chloroquine or monensin had little or no effect on CT stimulation of cyclic AMP accumulation, brefeldin A (BFA) totally inhibited the response to CT in a time- and dose-dependent and reversible manner. BFA was effective when added at the same time as CT and had an IC50 of 30 ng/ml. BFA did not alter cell surface GM1 as cells treated with BFA for 30 min bound as much 125I-CT as control cells. Furthermore, BFA inhibited CT stimulation of GM1-treated rat glioma C6 cells. BFA treatment did not affect beta-adrenergic agonist stimulation of cyclic AMP. In addition, adenylylcyclase was activated by A1 peptide and NAD+ to the same extent in membranes from control and BFA-treated cells, or when BFA was added directly to the assay. Whereas control cells generated small amounts of A1 from bound CT with time, no A1 was detected in BFA-treated cells. BFA treatment did not prevent the internalization of CT but did inhibit its degradation. BFA is known to disrupt the organization of the Golgi complex, resulting in inhibition of protein transport from the endoplasmic reticulum and redistribution of Golgi enzymes to the endoplasmic reticulum. BFA also prevents the formation of non-clathrin-coated vesicles from Golgi membranes and thus vesicular transport between Golgi cisternae. We confirmed that BFA caused the morphological disruption of the Golgi apparatus in Caco-2 cells. The data support a role for a functional Golgi apparatus with its associated vesicular routing in CT action.
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PMID:Brefeldin A blocks the response of cultured cells to cholera toxin. Implications for intracellular trafficking in toxin action. 838 69

Recent experiments indicate that the calcium store (e.g., endoplasmic reticulum) is involved in electrical bursting and [Ca2+]i oscillation in bursting neuronal cells. In this paper, we formulate a mathematical model for bursting neurons, which includes Ca2+ in the intracellular Ca2+ stores and a voltage-independent calcium channel (VICC). This VICC is activated by a depletion of Ca2+ concentration in the store, [Ca2+]cs. In this model, [Ca2+]cs oscillates slowly, and this slow dynamic in turn gives rise to electrical bursting. The newly formulated model thus is radically different from existing models of bursting excitable cells, whose mechanism owes its origin to the ion channels in the plasma membrane and the [Ca2+]i dynamics. In addition, this model is capable of providing answers to some puzzling phenomena, which the previous models could not (e.g., why cAMP, glucagon, and caffeine have ability to change the burst periodicity). Using mag-fura-2 fluorescent dyes, it would be interesting to verify the prediction of the model that (1) [Ca2+]cs oscillates in bursting neurons such as Aplysia neuron and (2) the neurotransmitters and hormones that affect the adenylate cyclase pathway can influence this oscillation.
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PMID:Modeling slowly bursting neurons via calcium store and voltage-independent calcium current. 869 30


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