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)

Stimulation of fatty acid biosynthesis by feeding high-carbohydrate diet to chickens after fasting induces a 38% and 23% rise in the 3':5'-cyclo-nucleotide phosphodiesterase and adenylate cyclase activities in the liver tissue, respectively. Administration of nicotinic acid (150 mg per 1 kg of weight) to chickens with stimulated biosynthesis of fatty acids leads to a sharp (70% at an average) decrease of 3':5'-cyclo-nucleotide phosphodiesterase activity, the adenylate cyclase activity under these conditions remains practically unchanged. The participation of the adenylate cyclase system in regulating the fatty acid biosynthesis under mentioned conditions, the role of phosphodiesterase are discussed.
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PMID:[Effect of nicotinic acid on phosphodiesterase and adenyl cyclase activities in chicken liver]. 629 Dec 7

The influence of N-ethylmaleimide and trypsin was studied on stimulatory and inhibitory regulations of the hamster adipocyte adenylate cyclase. Treatment of intact adipocytes or adipocyte ghosts with N-ethylmaleimide decreased basal and forskolin-stimulated adenylate cyclase activities. In the pretreated membrane preparations, inhibition of the enzyme by GTP and by stable GTP analogues was abolished. Concomitantly, activation of the adenylate cyclase by NaCl and its inhibition by the antilipolytic agents, prostaglandin E1 and nicotinic acid, were obliterated. In contrast, adenylate cyclase stimulation by ACTH and stable GTP analogues was not impaired but rather increased. Similarly, the NaCl-induced attenuation of the ACTH-stimulated enzyme activity was increased by the N-ethylmaleimide treatment. Limited proteolysis of hamster adipocyte ghosts with trypsin also obliterated GTP and prostaglandin E1-induced inhibitions and NaCl-induced activation of the adenylate cyclase. In contrast, adenylate cyclase activity stimulated by isoproterenol was increased after trypsin treatment. The data suggest that the activity of the adenylate cyclase is regulated via two distinct guanine nucleotide sites and that treatment with N-ethylmaleimide and limited proteolysis with trypsin functionally eliminates the regulatory site mediating adenylate cyclase inhibition, leading to a state where the enzyme activity is regulated only via the stimulatory site. The differential effects of these treatments on NaCl-induced activation and attenuation of the adenylate cyclase suggest that sodium acts on both regulatory sites in an inhibitory manner, and that by the functional elimination of the inhibitory site, only the sodium-induced attenuation of the adenylate cyclase via the stimulatory site is observed.
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PMID:Inactivation of the guanine nucleotide regulatory site mediating inhibition of the adenylate cyclase in hamster adipocytes. 630 Jun 99

Growth of Bordetella pertussis in a high concentration of nicotinic acid (NA) had a modulating effect on several properties and activities of the bacteria. Compared with normally grown cells, those grown in a high concentration of NA had reduced capacity for taking up both NA and nicotinamide (ND); they had reduced adenylate cyclase activity and showed loss of agglutinogen factors 2 and 3, but an increase in factor 1. By contrast, cells grown in a high concentration of ND showed only a slightly decreased capacity for uptake of ND and none of the other changes. Modulation of B. pertussis by NA varied with the strain and culture conditions and appeared to be distinct from the antigenic modulation induced by high Mg2+ in the culture medium. Evidence is presented for the association of a small proportion of the extracytoplasmic adenylate cyclase with the outer membrane of B. pertussis.
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PMID:Modulation of Bordetella pertussis by nicotinic acid. 630 72

Pertussis toxin was purified approx. 1800-fold from pertussis vaccine. Administration of as little as 1 microgram of toxin/100 g body weight to hamsters markedly decreased the sensitivity of their adipocytes to agents that inhibit adenylate cyclase through receptor-mediated, GTP-dependent mechanisms such as alpha 2-adrenergic amines, prostaglandins, phenylisopropyladenosine and nicotinic acid. On the contrary, the inhibitory effect of 2',5'-dideoxyadenosine on cyclic AMP accumulation was not affected by the toxin. Activation of adenylate cyclase by isoproterenol, ACTH or forskolin was not diminished by the toxin but the maximum cyclic AMP accumulation was consistently increased. Furthermore, the dose-response curves for ACTH and forskolin were clearly shifted to the left in adipocytes from toxin-treated hamsters as compared to control adipocytes. It is concluded that pertussis toxin blocks the transfer of inhibitory information from the receptors to adenylate cyclase.
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PMID:Effect of pertussis toxin on the hormonal regulation of cyclic AMP levels in hamster fat cells. 631 62

Incubation of pieces of adipose tissue in the presence of pertussis toxin (10-100 micrograms/ml) resulted in blockade in the isolated fat cells of the action of agents that inhibit adenylate cyclase through receptor-mediated GTP-dependent processes (alpha 2-adrenergic amines, prostaglandins, Ri-adenosine, nicotinic acid) and enhancement of the action of isoproterenol. There was a lag period of approximately 2 h for the action of the toxin.
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PMID:Direct action of pertussis toxin in isolated hamster fat cells. 632 35

In vivo administration of islet-activating protein to rats resulted in an increase in fat cell lipolysis in vitro, which was associated with almost complete resistance of adipocytes towards the antilipolytic effects of N6-phenylisopropyladenosine, prostaglandin E2 and nicotinic acid. Concomitantly, the inhibitory effects of these compounds on adenylate cyclase activity in membranes were impaired. In contrast, the antilipolytic action of insulin was not only preserved, but even augmented in cells from rats treated with islet-activating protein. The data suggest that insulin exerts its antilipolytic effects via mechanisms which are different from those involved in the effects of prostaglandin E2, N6-phenylisopropyladenosine and nicotinic acid.
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PMID:Islet-activating protein discriminates the antilipolytic mechanism of insulin from that of other antilipolytic compounds. 635 45

beta-Adrenergic agonists such as isoproterenol stimulate hamster adipocyte adenylate cyclase by a GTP-dependent process, whereas prostaglandin E1, alpha-adrenergic agonists, and nicotinic acid inhibit the enzyme by a process also dependent on GTP and amplified by sodium ions. We have determined the first-order rate constant describing the decay of isoproterenol plus GTP-stimulated adenylate cyclase and the modulation of this off rate constant by sodium and inhibitory hormonal factors. With 1 microM GTP and 0.2 mM isoproterenol, the off rate constant was 5.0 min-1 at 25 degrees C. Addition of NaCl (100 mM), which increased basal and isoproterenol-stimulated cyclase activities, decreased the rate constant of the hormone-stimulated enzyme to 1.4 min-1. Prostaglandin E1 (10 microM) and nicotinic acid (30 microM), which decreased basal and hormonally stimulated enzyme activities, increased the NaCl-suppressed off rate constant to 6.1 and 6.0 min-1, respectively. Similar data were obtained with 1 mM isoproterenol with MnATP and MgATP as the adenylate cyclase substrate. On the other hand, the turn-on reaction of adipocyte adenylate cyclase, measured with the stable GTP analogue 5'-guanylyl imidodiphosphate (30 microM), was accelerated by isoproterenol (1 mM) and NaCl (100 mM). Under all of these conditions, inhibitory hormonal agents did not cause any delay in the turn-on reaction. These data indicate that, in hamster adipocyte membranes, inhibitory hormonal factors inhibit adenylate cyclase by increasing the enzyme's turn-off reaction.
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PMID:Acceleration of the adipocyte adenylate cyclase turn-off reaction by inhibitory hormonal factors. 695 Nov 82

1. Bradykinin and related kinins possess two different types of action (consisting of relaxation and contraction) in the isolated rat duodenum via their specific receptors. However, the mechanisms of these actions have not been fully elucidated. The present study was undertaken to investigate the effects of the agents affecting cyclic nucleotide metabolism on bradykinin-induced relaxations and on bradykinin- and des-Arg9-bradykinin-induced contractions. 2. Des-Arg9-bradykinin, B1 receptor agonist, and high concentrations of bradykinin elicited dose-dependent contractile responses in the rat duodenum, while low concentrations of bradykinin caused a dose-dependent relaxation in this tissue. 3. Nicotinic acid, an inhibitor of adenylate cyclase, inhibited the relaxation of rat duodenum induced by bradykinin at low concentrations in a non-competitive manner. However, the inhibitory efficacy of nicotinic acid against bradykinin was limited by 39.9% and this inhibition was not further increased by higher concentrations of nicotinic acid up to 10(-3) M. 4. Imidazole, an activator of cyclic nucleotide phosphodiesterase, caused a slight inhibition of the relaxant responses to low concentrations of bradykinin and of the contractile responses to des-Arg9-bradykinin and high concentrations of bradykinin in isolated rat duodenum. These inhibitions were also limited in efficacies and not increased by higher concentrations of imidazole. 5. Methylene blue, an agent that inhibits soluble guanylate cyclase, suppressed the contractions of rat duodenum induced by des-Arg9-bradykinin and high concentrations of bradykinin in a non-competitive manner. Again, these inhibitions were limited and further increase in the inhibitory efficacy was not observed in spite of increasing the methylene blue concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of the agents affecting cyclic nucleotide metabolism on the bradykinin- and des-Arg9-bradykinin-induced relaxations and contractions in isolated rat duodenum. 789 50

Expression of granulocyte-macrophage colony-stimulating factor (GM-CSF) by metastatic Lewis lung carcinoma cells (LLC-LN7) was previously shown to contribute to the maintenance of phenotypic characteristics associated with an increased capacity to metastasize. In the present study, pre-incubation of LLC-LN7 cells with neutralizing anti-GM-CSF antibodies diminished the capacity of the tumor cells to form experimental metastases after i.v. inoculation, while pre-incubation with recombinant GM-CSF (rGM-CSF) increased formation of metastases. In the presence of rGM-CSF, the LLC-LN7 cells exhibited an increased capacity to migrate, invade through a reconstituted basement membrane, and adhere to lung tissue. Studies to identify the signal transduction pathway through which GM-CSF enhanced the in vitro metastatic properties of the LLC-LN7 tumor cells implicated protein kinase A (PKA). Signaling through PKA was suggested by the demonstration that the stimulation of tumor-cell motility by GM-CSF was blocked in the presence of the adenylate cyclase inhibitor nicotinic acid, or the PKA inhibitors A3 or KT5720. In addition, the role of PKA as a signaling mechanism for GM-CSF was assessed by using REV-LN7 cells, which are LLC-LN7 cells that have been stably transfected with an expression vector encoding a mutant PKA RI alpha subunit and which, in turn, express a cAMP-resistant PKA. Adherence and invasion by the PKA-defective REV-LN7 cells were not stimulated by rGM-CSF, contrasting with the stimulation observed for wild-type LLC-LN7 cells. These data suggest that rGM-CSF can further enhance the in vitro metastatic characteristics of LLC-LN7 tumor cells and that this is dependent on signal transduction through PKA.
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PMID:Granulocyte-macrophage colony-stimulating factor stimulates the metastatic properties of Lewis lung carcinoma cells through a protein kinase A signal-transduction pathway. 843 41

The inhibition of alpha i2-/- mouse cardiac isoproterenol-stimulated adenylyl cyclase (AC; EC 4.6.1.1) activity by carbachol and that of alpha i2-/- adipocyte AC by phenylisopropyladenosine (PIA), prostaglandin E2, and nicotinic acid were partially, but not completely, inhibited. While the inhibition of cardiac AC was affected in all alpha i2-/- animals tested, only 50% of the alpha i2-/- animals showed an impaired inhibition of adipocyte AC, indicative of a partial penetrance of this phenotype. In agreement with previous results, the data show that Gi2 mediates hormonal inhibition of AC and that Gi3 and/or Gi1 is capable of doing the same but with a lower efficacy. Disruption of the alpha i2 gene affected about equally the actions of all the receptors studied, indicating that none of them exhibits a striking specificity for one type of Gi over another and that receptors are likely to he selective rather than specific in their interaction with functionally homologous G proteins (e.g., Gi1, Gi2, Gi3). Western analysis of G protein subunit levels in simian virus 40-transformed primary embryonic fibroblasts from alpha i2+/+ and alpha i2-/- animals showed that alpha i2 accounts for about 50% of the immunopositive G protein alpha subunits and that loss of the alpha i2 is accompanied by a parallel reduction in G beta 35 and G beta 36 subunits and by a 30-50% increase in alpha i3. This suggests that G beta-gamma levels may be regulated passively through differential rates of turnover in their free vs. trimeric states. The existence of compensatory increase(s) in alpha i subunit expression raises the possibility that the lack of effect of a missing alpha i2 on AC inhibition in adipocytes of some alpha i2-/- animals may be the reflection of a more pronounced compensatory expression of alpha i3 and/or alpha i1.
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PMID:Adenylyl cyclase inhibition and altered G protein subunit expression and ADP-ribosylation patterns in tissues and cells from Gi2 alpha-/-mice. 862 15


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