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)

The effect of neuropeptide Y (NPY) on adenylate cyclase activity and the role of G-proteins mediating NPY's effect were investigated in cultured bovine adrenal chromaffin cells. The equilibrium binding of [125I]NPY to sucrose gradient purified bovine adrenal medulla plasma membranes revealed high- (GTP gamma S sensitive) and low-affinity binding sites with calculated IC50 values of 0.27 nM and 0.14 microM, respectively. Inhibition of forskolin-stimulated cyclic AMP accumulation was dependent upon the NPY concentration (IC50 = 0.9 nM) and independent of cyclic AMP (cAMP) phosphodiesterase activity. NPY-related peptides, except peptide YY, and NPY fragments exhibited minimal inhibitory activity. The inhibitory effect of NPY on forskolin-stimulated adenylate cyclase activity was completely abolished by pretreatment of the cells with pertussis toxin (PTX). Incubation of membranes with PTX and [32P]nicotinamide adenine dinucleotide revealed a protein band with an apparent molecular mass of 41 kDa. The time course and dose dependence of PTX pretreatment for in vitro ADP-ribosylation were similar to those for PTX to attenuate the NPY effect on forskolin-stimulated adenylate cyclase activity. The direct relation between the NPY receptor and the PTX-sensitive G-protein was further shown by the ability of NPY to inhibit PTX-catalyzed in vitro ADP-ribosylation. ADP-ribosylation of the 41-kDa protein was partially inhibited by 5'-guanylylimidodiphosphate and further inhibited by high concentrations of NPY. An antibody against Gi1/i2 alpha 1 recognized two species of which a 41-kDa protein comigrated with the PTX substrate.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Neuropeptide Y inhibits forskolin-stimulated adenylate cyclase in bovine adrenal chromaffin cells via a pertussis toxin-sensitive process. 133 68

Four ADP-ribosyltransferases that acted on non-muscle actin were purified more than 3,000-fold from rat brain extract. The molecular weights of these brain ADP-ribosyltransferases were 66,000 as estimated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and gel filtration on TSK gel G3000SW. The Km values for NAD were approximately 20 microM. These enzymes were not inhibited by thymidine or nicotinamide, but were inhibited by ADP and ADP-ribose. Two soluble ADP-ribosylation factors purified from rat brain had different effects on the four ADP-ribosyltransferases during the ADP-ribosylation of non-muscle actin. These ADP-ribosyltransferases modified not only actin but also the stimulatory guanine nucleotide-binding protein of adenylate cyclase, Gs, and another guanine nucleotide-binding protein in brain, Go. These findings suggest that the four brain ADP-ribosyltransferases are concerned with nerve functions in the central nervous system.
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PMID:Mono-ADP-ribosylation in brain: purification and characterization of ADP-ribosyltransferases affecting actin from rat brain. 191 76

Islet-activating protein (IAP), one of the pertussis toxins, serving [alpha-32P]nicotinamide adenine dinucleotide (NAD) as a substrate for ADP ribosylation, radiolabelled a specific pig epidermal membrane protein. The IAP-specific substrate was detectable by sodium dodecyl sulphate-polyacrylamide gel electrophoresis as a single band corresponding to a molecular weight of 40 kDa. The ADP ribosylation catalysed by IAP was inhibited by the addition of Mg2+ to the reaction mixture. IAP is known to work on intact cell systems resulting in the ADP ribosylation using intracellular NAD as the ADP ribose donor. Following IAP pretreatment of intact pig epidermis, the epidermal receptor adenylate cyclase responses were markedly increased; all the stimulatory receptor adenylate cyclase responses (beta-adrenergic, prostaglandin E, adenosine and histamine responses) were significantly increased. Cholera toxin-induced cyclic AMP accumulation was also significantly increased. Forskolin-induced cyclic AMP accumulation was slightly increased after IAP pretreatment, but this was not statistically significant. The IAP-dependent ADP ribosylation of the epidermal 40 kDa membrane protein, which was prepared from the IAP pretreated epidermis, was significantly decreased. It is known that the tumour promoter, phorbol 12-myristate,13-acetate (PMA), decreases stimulatory receptor adenylate cyclase responses of the epidermis. Following the PMA pretreatment, IAP-dependent ADP ribosylation of the epidermal membrane protein was unaffected. Furthermore, following the PMA pretreatment, the IAP-induced increase in the epidermal receptor adenylate cyclase responses still remained. Our results indicate that pig epidermis contains 40 kDa membrane substrate for IAP-dependent ADP ribosylation, which has an inhibitory tonus on the epidermal adenylate cyclase until its ADP ribosylation by IAP.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Inhibitory guanine nucleotide binding protein in pig epidermis: regulation of epidermal adenylate cyclase. 196 35

1. Cholera toxin (1 microgram/ml) abolished net fluid absorption by everted sacs of rabbit ileum, leading to net fluid secretion. This action occurred via the toxin-catalysed ADP ribosylation of the stimulatory GTP-binding protein Gs which is linked to adenylate cyclase. Nicotinamide (10 mM), a reaction product of ADP ribosylation, reversed cholera toxin-induced secretion, restoring absorption. Lower concentrations of nicotinamide induced partial reversal. 2. Nicotinamide (1 mM) blocked the secretory action of cholera toxin applied to ileal sacs. This inhibitory action was more effective in the presence of methionine (1 mM). 3. Other inhibitors of ADP ribosylation, benzamide and adenine, blocked the secretory action of cholera toxin. Hypoxanthine, an analogue and metabolite of adenine, was similarly effective. 4. Nicotinamide was not, however, effective in blocking or reversing the secretory action of theophylline (10 mM) or of heat-stable E. coli enterotoxin STa. This indicates that nicotinamide has a highly specific action against ADP ribosylating toxins. 5. It is proposed that nicotinamide reverses the secretory action of cholera toxin by reversing ADP ribosylation, simply by the law of mass action. This counters the established idea that the effects of cholera and other ADP-ribosylating toxins are irreversible under physiological conditions.
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PMID:Reversal and inhibition of cholera toxin-induced secretion in isolated rabbit ileum. 214 Aug 61

Treatment of platelets with a prostacyclin analogue, iloprost, decreased the cholera-toxin-induced ADP-ribosylation of membrane-bound Gs alpha (alpha-subunit of G-protein that stimulates adenylate cyclase; 42 kDa protein) and a cytosolic substrate (44 kDa protein) [Molina y Vedia, Reep & Lapetina (1988) Proc. Natl. Acad. Sci. U.S.A. 85, 5899-5902]. This decrease is apparently not correlated with a significant change in the quantity of membrane Gs alpha, as detected by two Gs alpha-specific antisera. This finding contrasts with the suggestion in a previous report [Edwards, MacDermot & Wilkins (1987) Br. J. Pharmacol. 90, 501-510], indicating that iloprost caused a loss of Gs alpha from the membrane. Our evidence points to a modification in the ability of the 42 kDa protein to be ADP-ribosylated by cholera toxin. This modification of Gs alpha might be related to its ADP-ribosylation by endogenous ADP-ribosyltransferase activity. Here we present evidence showing that Gs alpha was ADP-ribosylated in platelets that had been electropermeabilized and incubated with [alpha-32P]NAD+. This endogenous ADP-ribosylation of Gs alpha is inhibited by nicotinamide and stimulated by iloprost.
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PMID:The effect of iloprost on the ADP-ribosylation of Gs alpha (the alpha-subunit of Gs). 247 20

The heat-stable enterotoxin (STa) of E. coli activates intestinal guanylate cyclase and leads to increased cGMP levels by an as yet undetermined mechanism. In comparing this cGMP system to other known toxin-mediated alterations in cAMP metabolism, we observed that pertussis toxin caused lower levels of intestinal cGMP synthesis in response to purified STa. Another participant in ADP-ribosylation reactions, NAD, enhanced the ability of STa to activate guanylate cyclase, yet had no effect on basal enzyme activity. Niacinamide and isoniacinamide also had no effect on basal activity, but attenuated the STa activation. These results are discussed in relation to current models of hormone/toxin-sensitive adenylate cyclase, and may suggest an involvement of guanine-nucleotide-binding proteins in intestinal cGMP metabolism.
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PMID:Activation of guanylate cyclase by E. coli heat-stable enterotoxin (STa). Modulation by NAD and pertussis toxin. 287 59

NAD+ significantly enhances adenylate cyclase activity in crude cardiac membrane preparations. This increase is dose-dependent, does not occur in the presence of nicotinamide, ADP-ribose or NADP+, and can be effected by a 30 min pre-incubation period with NAD+. Time course studies are consistent with an enzymatically mediated modification that used NAD+ as substrate. Furthermore, inhibition of NAD+-mediated activation by arginine suggests that this modulation of cardiac adenylate cyclase is analogous to that catalyzed by endogenous ADP-ribosyl transferases.
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PMID:NAD+-mediated stimulation of adenylate cyclase in cardiac membranes. 295 Aug 54

We examined Bordetella avium for virulence factors common to Bordetella pertussis, including pertussis toxin, filamentous hemagglutinin, adenylate cyclase, dermonecrotic toxin, and tracheal cytotoxin. B. avium produced a dermonecrotic toxin and a tracheal cytotoxin. The dermonecrotic toxin of B. avium is a 155,000-molecular-weight, heat-labile protein which was lethal for mice, guinea pigs, young chickens, and turkey poults and produced dermonecrosis when injected intradermally into guinea pigs, chickens, and turkey poults. High-pressure liquid chromatography of B. avium culture supernatant fluid revealed the presence of a tracheal cytotoxin chemically identical to that produced by B. pertussis. B. avium isolates were negative for B. pertussis-like filamentous hemagglutinin and pertussis toxin when assayed with antibody against B. pertussis filamentous hemagglutinin and pertussis toxin. Furthermore, B. avium failed to induce the clustered CHO cell morphology characteristic of pertussis toxin. Adenylate cyclase assays indicated that B. avium does not produce an extracytoplasmic adenylate cyclase, even after passage through embryonated turkey eggs. Since production of virulence proteins by B. pertussis is regulated by growth in media containing nicotinamide or MgSO4 or by growth at reduced temperatures, we determined the effect of these supplements and growth conditions on production of dermonecrotic toxin by B. avium. Production of dermonecrotic toxin in B. avium was not altered by growth in media containing 100 microM FeSO4 or 500 micrograms of nicotinamide per ml or by growth at 25 or 42 degrees C, but production was significantly decreased by growth in media containing 20 mM MgSO4 and slightly reduced by growth in media containing 500 micrograms of nicotinic acid per ml. These studies revealed that B. avium is similar to B. pertussis in that both species produce a dermonecrotic toxin and a tracheal cytotoxin and production of dermonecrotic toxin is regulated by nicotinamide and MgSO4. The presence of dermonecrotic toxin and tracheal cytotoxin in all Bordetella species indicates that these products may be important virulence factors in bordetellosis.
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PMID:Dermonecrotic toxin and tracheal cytotoxin, putative virulence factors of Bordetella avium. 338 73

Cyclic adenosine 3',5'-monophosphate (cAMP) plays a critical role in modulating a variety of neuronal responses in Aplysia californica. Previous studies have focused on the neurotransmitter activation of adenylate cyclase, which presumably occurs via the guanosine 5'-triphosphate (GTP)-regulated excitatory subunit (Ns). While adenylate cyclase has also been shown to be regulated by inhibitory neurotransmitters, coupled through the inhibitory GTP-regulated coupling protein Ni in some systems, the effects of Ni-mediated adenylate cyclase inhibition on neuronal processing in Aplysia have not previously been reported. In the present study Ni is detected in Aplysia by both protein chemistry and enzymatic activity. A 40 kdalton substrate for the enzymatic activity of Bordetella pertussis toxin is observed. Incubation of Aplysia nervous tissue homogenates with pertussis toxin (IAP) and 32P-nicotinamide-adenine dinucleotide labels a single protein, assessed by polyacrylamide gel electrophoresis and autoradiography. Furthermore, crude membrane suspensions of this tissue demonstrate biphasic adenylate cyclase activity in response to increasing concentrations of GTP, showing Ni and Ns functional activities. These findings provide evidence that Ni is present in Aplysia tissue. Ni may serve as an important site for the regulation of cAMP synthesis and neuronal plasticity.
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PMID:Evidence for the inhibitory subunit of adenylate cyclase (Ni) in nervous and heart tissue of Aplysia. 396 Mar 97

A rapid method of preparing plasma membranes from isolated fat cells is described. After homogenization of the cells, various fractions were isolated by differential centrifugation and linear gradients. Ficoll gradients were preferred because total preparation time was under 3 hr. The density of the plasma membranes was 1.14 in sucrose. The plasma membrane fraction was virtually uncontaminated by nuclei but contained 10% of the mitochondrial succinic dehydrogenase activity and 25-30% of the RNA and reduced nicotinamide adenine dinucleotide cytochrome c reductase activity of the microsomal fraction. Part of the RNA and NADH-cytochrome c reductase activity was believed to be native to the plasma membrane or to the attached endoplasmic reticulum membranes demonstrated by electron microscopy. The adenyl cyclase activity of the plasma membrane fraction was five times that of Rodbell's "ghost" preparation and retained sensitivity to epinephrine. The plasma membrane ATPase activity was five times that of the homogenate and microsomal fractions. Electron microscopic evidence suggested contamination of the plasma membrane fraction by other subcellular components to be less than the biochemical data indicated.
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PMID:Preparation and characterization of a plasma membrane fraction from isolated fat cells. 424 33


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