Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.6.1.1 (adenylate cyclase)
 19,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The cytochemical localization of adenylate cyclase and guanylate cyclase was studied in the arteries of the circle of Willis in dogs. The reaction products of both adenylate and guanylate cyclases were similarly distributed and selectively localized predominantly adjacent to sarcoplasmic reticulum and sparsely to mitochondria and outer nuclear membranes of vascular smooth muscles. The observations could suggest a close association of the intracellular localizations of both cyclases and the intracellular calcium storage sites, and ultimately contribute to our complete understanding of regulation of cerebral blood flow and vasospasm.
 ...
PMID:Cytochemical demonstration of adenylate and guanylate cyclases in vascular smooth muscle of circle of Willis. 2 90

Behavioral sensitization of the gill-withdrawal reflex of Aplysia is the result of a prolonged increase in transmitter release from the presynaptic terminals of sensory neurons. Earlier work suggested that this presynaptic facilitation might be mediated by a serotonin-sensitive adenylate cyclase in the sensory neuron terminals. Here we present evidence that presynaptic facilitation results from a cyclic AMP-dependent increase in the calcium current that underlies action potentials in the sensory neurons. The action potentials of sensory neuron cell bodies have, in addition to a sodium current, a calcium current that is enhanced by blocking the opposing potassium current with tetraethylammonium. Under these conditions, the action potentials show a slowly repolarizing plateau that follows the Nernst potential for a calcium electrode and serves as a sensitive assay for changes in calcium current. Stimulation of the pathway that mediates sensitization, incubation with serotonin or phosphodiesterase inhibitors, or intracellular injection of cyclic AMP produces an increase in the calcium plateau in the presence of tetraethylammonium. In addition, both before and after sensitizing stimulation, the duration of the plateau potential parallels transmitter release as measured by the amplitude of monosynaptic excitatory postsynaptic potentials evoked in the motor neurons by intracellular stimulation of single sensory neurons. These results are consistent with the idea that presynaptic facilitation is caused by a cyclic AMP-mediated increase in a voltage-sensitive calcium current in sensory neuron presynaptic terminals. This synaptic action is novel in that it can produce little or no change in the resting potential, is of long duration, and exerts its influence directly on a conductance triggered by the action potential, rather than on non-voltage-sensitive conductances, as is typical of conventional synaptic actions.
 ...
PMID:Presynaptic modulation of voltage-dependent Ca2+ current: mechanism for behavioral sensitization in Aplysia californica. 2 27

1. The adenylate cyclase in Trypanosoma brucei is located in the plasma membrane. 2. A partial kinetic analysis of the properties of the enzyme revealed a Km for ATP of 1.75 mM and a Km for Mg2+ of 4mM. 3. At low concentrations, Mg2+ activated the enzyme directly in addition to its effect of lowering the concentration of inhibitory free ATP species. 4. At high concentrations, Mg2+ inhibited the enzyme. Furthermore, the enzyme was inhibited at any Mg2+ concentration if the concentration of ATP exceeded that of Mg2+. 5. The opposing effects of Mg2+ at low and high concentrations would be consistent with more than one binding site for Mg2+ on the enzyme. 6. A study of the patterns of product inhibition revealed little or no effect of 3':5'-cyclic AMP, but a profound inhibition by pyrophosphate, which was competitive with respect to ATP (Ki 0.135 mM). This result suggests that the substrate-binding domain on T. brucei adenylate cyclase interacts mainly with the triphosphate portion of the ATP molecule. 7. The enzyme activity was unaffected by the usual mammalian enzyme effectors glucagon, adrenaline, adenosine, GTP and guanyl-5'-yl imidodiphosphate. 8. The enzyme was not activated by fluoride, instead a powerful inhibition was found. The enzyme was also inhibited by relatively high concentrations of Ca2+ (1 mM).
 ...
PMID:Adenylate cyclase in bloodstream forms of Trypanosoma (Trypanozoon) brucei sp. 3 75

1. Heterosynaptic facilitation (modification of synaptic transmission by a neuron influencing the terminals of the presynaptic neuron) was studied in the pleural ganglion of Aplysia. Among several identified synapses, heterosynaptic facilitation was observed only in one type (EIPSP synapses) when repetitive stimulation was applied to the tentacular nerve or to a particular identified neuron. 2. Serotonin was shown to increase the amplitude of the EIPSP at this synapse; this facilitatory effect was prolonged in the presence of theophylline and mimicked by cyclic AMP. 3. When transmission was abolished by calcium-free solution, calcium injected in the region of the synapse caused partial recovery of the EIPSP; when calcium injection was preceded by serotonin injection near the same terminal, the EIPSP was much larger than with calcium injection alone. 4. It was concluded that the activation of one neuron (the heterosynaptic neuron) caused it to release serotonin, which activated an adenylate cyclase in the pre-synaptic terminals of another neuron. Consequent accumulation of cyclic AMP in these terminals is supposed to have increased their voltage-dependent calcium conductance and hence the amount of transmitter released during an action potential.
 ...
PMID:The role of cyclic AMP in the modulation of synaptic efficacy. 3 32

Guanylate cyclase [EC 4.6.1.2] activity in Tetrahymena pyriformis cells was associated with particulate fractions, but not with soluble fractions. Mg2+ was much more effective than Mn2+ in activating the cyclase activity. Both specific and total cyclase activities with Mg2+ in the particulate fraction were very much lower than those in the original homogenate. The addition of the soluble fraction resulted in a marked enhancement of the particulate-bound cyclase activity, while the adenylate cyclase [EC 4.6.1.1] activity was not enhanced. The enhancement was dependent on Ca2+, and the activating factor is suggested to be a protein.
 ...
PMID:Magnesium-sensitive guanylate cyclase and its endogenous activating factor in Tetrahymena pyriformis. 3 68

The guanylate cyclase activity of axoneme--basal apparatus complexes isolated from bovine retinal rods has been investigated. The Mg2+ and Mn2+ complexes of GTP4- serve as substrates. Binding of an additional mole of Mg2+ or Mn2+ per mole of enzyme is required. Among cations which are ineffective are Ca2+, Ni2+, Fe2+, Fe3+, Zn2+, and Co2+. The kinetics are consistent with a mechanism in which binding of Mg2+ or Mn2+ to the enzyme must precede binding of MgGTP or MnGTP. The apparent dissociation constants of the Mg--enzyme complex and the Mn--enzyme complex are 9.5 x 10(-4) and 1.1 x 10(-4) M, respectively. The apparent dissociation constants for binding of MgGTP and MnGTP to the complex of the enzyme with the same metal are 7.9 x 10(-4) and 1.4 x 10(-4) M, respectively. The cyclase activity is maximal and independent of pH between pH 7 and 9. KCl and NaCl are stimulatory, especially at suboptimal concentrations of Mg2+ or Mn2+. Ca2+ and high concentrations of Mg2+ and Mn2+ are inhibitory. Ca2+ inhibition appears to require the binding of 2 mol of Ca2+ per mol of enzyme. The dissociation constant of the Ca2--enzyme complex is estimated to be 1.4 x 10(-6) M2. The axoneme--basal apparatus preparations contain adenylate cyclase activity whose magnitude is 1--10% that of the guanylate cyclase activity.
 ...
PMID:Guanylate cyclase of isolated bovine retinal rod axonemes. 4 May 95

Aggregating cells of Dictyostelium discoideum are able to release cyclic AMP periodically. The oscillations of cAMP generation are associated with changes in adenylate cyclase activity. Cyclic AMP receptors on the cell surface are functionally coupled to the oscillating system as evidenced by phase shifts that are induced by small pulses of extracellular cAMP. An important element of the oscillating system is the signal processing from surface receptors to the adenylate cyclase. This pathway exhibits adaptation resulting in the suppression of responses to constant, elevated concentrations of cAMP. The signal input for adenylate cyclase activation is, therefore, a change in the extracellular cAMP concentration with time. Oscillations in the absence of detectable changes of intra- or extracellular cAMP concentrations suggest the possibility that there is a metabolic network in D. discoideum cells that undergoes oscillations without coupling to adenylate cyclase. Cyclic GMP concentrations oscillate with a slight phase difference in advance of that of cAMP, suggesting that the two nucleotide cyclases might not be activated by the same mechanism. Elevation of extracellular calcium exerts an inhibitory effect on the accumulation of cAMP and on the second of the two cGMP peaks.
 ...
PMID:Oscillations of cyclic nucleotide concentrations in relation to the excitability of Dictyostelium cells. 4 79

The accumulation of cyclic adenosine 3',5'-monophosphate (cAMP) in guinea-pig macrophages exposed to the adenylate cyclase (AC) stimulators prostaglandin E1 (PGE1) and isoproterenol (IP), was markedly enhanced by pretreatment of the cells with colchicine, vinblastine, and podophyllotoxin--agents which prevent microtubule assembly. The same agents did not augment basal cAMP levels. The facilitating effect of the drugs on the response to PGE1 and IP developed both in the absence and presence of a phosphodiesterase (PDE) inhibitor. The same drugs also enhanced the accumulation of cAMP induced by cholera toxin (CT) but the presence of a PDE inhibitor was required for such enhancement to become evident. Pretreatment of macrophages with cytochalasin B, an agent interfering with microfilament function, had no effect on the responsiveness of the cells to AC stimulators. The microtubule stabilizer, deuterium oxide (D2O) partially reversed the colchicine effect. Microtubule disrupting drugs did not block the release of cAMP from the cells into the surrounding medium. Macrophages incubated as monolayers or in suspension showed the same degree of increased responsiveness to stimulators after preexposure to colchicine. Preincubation with the ionophore A23187, which elevates the intracellular concentration of Ca2+, also enhanced the stimulation of AC by PGE1 and IP. Microtubule disrupting agents did not potentiate AC activity in broken cell preparations, whether added to the intact cells before disruption or directly to the enzyme assay mixture, nor did they affect PDE activity of macrophage sonicates. Moderate enhancement of PGE1-induced cAMP formation was also seen in colchicine- and vinblastine-treated lymphocytes. It was concluded that microtubules control the activity of AC by restricting the mobility of membrane receptors. Disruption of microtubules by drugs results in the removal of such restraints and an augmented chance of productive interactions between receptors and catalytic units of AC.
 ...
PMID:Enhancement of macrophage adenylate cyclase by microtubule disrupting drugs. 4 91

Retro-orbital tissue membranes have been shown to have adenylate cyclase activity which can be stimulated by thyrotropin and by an exophthalmogenic factor derived from the thyrotropin molecule by partial pepsin digestion. This stimulable activity is maximal after 15 min and is optimal in the presence of 3 mM magnesium and 1.5 mM ATP. Calcium salts are exquisitely inhibitory to the hormonal stimulation; sodium, lithium, and ammonium salts are significantly less inhibitory. Thyrotropin and the exophthalmogenic factor induce similar maximal levels of stimulation but a 4- to 5-fold higher concentration of exophthalmogenic factor is required to achieve this level. Fluoride stimulates adenylate cyclase activity 2- to 3-fold higher than either thyrotropin or the exophthalmogenic factor; thyrotropin, luteinizing hormone, the beta subunit of thyrotropin, and the alpha subunit of thyrotropin have relative activities for stimulation of cyclase activity of 100:2:2 less than 0.5. Several other polypeptide and glycoprotein hormones have no effect. The gamma-globulin from patients with malignant exophthalmos has no significant effect on cyclase activity either alone or in the presence of maximal levels of thyrotropin or the exophthalmogenic factor; this gamma-globulin does, however, stimulate cyclase activity at submaximal hormone levels. Trypsin not only destroys the hormone-stimulable adenylate cyclase activity on retro-orbital tissue plasma membranes, but also destroys it on the 15,000 to 30,000 molecular weight receptor fragment released from the membranes by the tryptic action.
 ...
PMID:Stimulation of adenylate cyclase activity in retro-orbital tissue membranes by thyrotropin and an exophthalmogenic factor derived from thyrotropin. 5 Oct 22

Cyclic AMP has been implicated in the regulation of the immunologic release of histamine from lung and other tissues and cell types. The mechanism whereby intracellular levels of cAMP are altered during mediator release was investigated. Measurements of histamine, adenylate cyclase, and cAMP phosphodiesterase activities were made in actively and passively sensitized guinea pig lung after challenge with antigen. A transient decrease in basal adenylate cyclase activity occurred which returned to control levels after histamine release. There was no change in cAMP phosphodiesterase activity determined at substrate concentrations of 1 mM and 0.01 mM. The adenylate cyclase response did not occur under the following conditions: 1) incubation of nonsensitized lung with antigen, 2) incubation of sensitized lung with antigen in the absence of extracellular calcium, and 3) incubation of nonsensitized lung with compound 48/80. These observations indicate 1) the adenylate cyclase response and the immunologic release of histamine are intimately related, and 2) the reduction in intracellular levels of cAMP which have been reported to occur during immunologic histamine release are mediated via adenylate cyclase.
 ...
PMID:Reduction in basal adenylate cyclase activity during the immunologic release of histamine from guinea pig lung. 6 29


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