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 conversion of phosphatidylethanolamine (PE) to phosphatidylcholine (PC) is catalyzed by two methyltransferases with S-adenosylmethionine as the methyl donor. PC formed by transmethylation is further metabolized by phospholipase A2. The synthesis and degradation of methylated phospholipids are involved in regulating the number of the beta-adrenergic receptors and their coupling to adenylate cyclase in rat reticulocytes, HeLa cells, and rat astrocytoma cells. Methylation of the phospholipids in these cells is stimulated by binding of agonists to the beta-adrenergic receptors. Accumulation of phosphatidyl-N-monomethylethanolamine causes an increase in membrane fluidity and enhances the coupling of the receptors to adenylate cyclase. Agents that inhibit phospholipid methylation decrease the number of receptors in intact HeLa cells, while increased phospholipid methylation unmasks cryptic receptors. Conversely, the degradation of methylated phospholipids appears to be closely associated with the desensitization of the beta-adrenergic receptors following prolonged stimulation with isoproterenol. Inhibition and stimulation of phospholipase A2 causes inhibition and stimulation of this desensitization process.
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PMID:Phospholipid methylation: a possible mechanism of signal transduction across biomembranes. 627 27

The specific binding of IgG2a or IgG2b subclass monoclonal anti-sheep erythrocyte antibodies to P388D1 cell surface Fc gamma 2aR3 or Fc gamma 2bR, respectively, triggered the synthesis of adenosine-3'5'-monophosphate (cAMP) to an approximately same extent by the mechanisms that are apparently unique for each type of Fc gamma Rs. Fc gamma 2aR appeared to trigger directly, upon binding of IgG2a antibodies, the adenylate cyclase system without requiring the participation of guanine nucleotide-binding (G/F) regulatory protein, because the Fc gamma 2aR-triggered cAMP synthesis, which reached maximum within 30 min, was not significantly affected by an uncoupler, Mn++ or by addition of guanosine triphosphate (GTP) analog, 5'-guanylylimidodiphosphate (Gpp(NH)p). In contrast, Fc gamma 2bR appeared to stimulate indirectly the G/F regulatory requiring-adenylate cyclase system by generating prostaglandins, since the cAMP synthesis, which required 90 min to reach plateau after binding of IgG2b to Fc gamma 2bR, was totally suppressed by phospholipase A2 inhibitor (p-bromophenacylbromide) or cyclo-oxygenase inhibitor (indomethacin), partially suppressed by Mn++, and slightly increased by Gpp(NH)p. Furthermore, the inhibition of phagocytic process by cytochalasin D increased cAMP synthesis mediated by Fc gamma 2aR (about 70% at 2 micrograms/ml), but did not affect Fc gamma 2bR-mediated cAMP synthesis. In addition, our data suggested that both Fc gamma 2aR- and Fc gamma 2bR-mediated cAMP synthesis are independent from beta-adrenergic receptor-mediated stimulation of the adenylate cyclase system, since either beta-agonist (isoproterenol) or beta-antagonist (propranolol) did not affect significantly the levels of cAMP produced in response to EA-stimulation.
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PMID:Biochemical signals transmitted by Fc gamma receptors: triggering mechanisms of the increased synthesis of adenosine-3',5'-cyclic monophosphate mediated by Fc gamma 2a- and Fc gamma 2b- -receptors of a murine macrophage-like cell line (P388D1). 629 97

The role of membrane phospholipids in enkephalin receptor-mediated inhibition of adenylate cyclase (EC 4.6.1.1) activity in neuroblastoma X glioma NG108-15 hybrids was studied by selective hydrolysis of lipids with phospholipases. When NG108-15 cells were treated with phospholipase C from Clostridium welchii at 37 degrees C, an enzyme concentration--dependent decrease in adenylate cyclase activity was observed. The basal and prostaglandin E1 (PGE1)-stimulated adenylate cyclase activities were more sensitive to phospholipase C (EC 3.1.4.3) treatment than were the NaF-5'-guanylylimidodiphosphate (Gpp(NH)p)-sensitive adenylate cyclase activities. Further, Leu5-enkephalin inhibition of basal or PGE1-stimulated adenylate cyclase activity was attenuated by phospholipase C treatment, characterized by a decrease of enkephalin potency and of maximal inhibitory level. [3H]D-Ala2-Met5-enkephalinamide binding revealed a decrease in receptor affinity with no measurable reduction in number of binding sites after phospholipase C treatment. Although opiate receptor was still under the regulation of guanine nucleotide after phospholipase C treatment, adenylate cyclase activity was more sensitive to the stimulation of Gpp(NH)p. Thus, the reduction of opiate agonist affinity was not due to the uncoupling of opiate receptor from N-component. Further, treatment of NG108-15 hybrid cell membrane with phospholipase C at 24 degrees C produced analogous attenuation of enkephalin potency and efficacy without alteration in receptor binding. The reduction in enkephalin potency could be reversed by treating NG108-15 membrane with phosphatidylcholine, but not with phosphatidylserine, phosphatidylinositol, or cerebroside sulfate. The enkephalin activity in NG108-15 cells was not altered by treating the cells with phospholipase A2 o phospholipase C from Bacillus cereus. Hence, apparently, there was a specific lipid dependency in enkephalin inhibition of adenylate cyclase activity.
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PMID:Attenuation of enkephalin activity in neuroblastoma X glioma NG108-15 hybrid cells by phospholipases. 629 48

In vitro, the cannabinoids delta 9-tetrahydrocannabinol (delta 9-THC), 11-OH-delta 9-THC, cannabidiol and cannabinol all increased adenylate cyclase activity in mouse cerebral cortical homogenates. Levonantradol, a synthetic cannabinoid analog, also increased adenylate cyclase activity while its optical isomer dextronantradol did not. The increases in enzyme activity produced by the active compounds were biphasic with significant increases at 10 microM and/or 30 microM concentrations with return to control levels at 100 microM. The increases did not occur in the absence of added GTP nor did delta 9-THC have any effect on fluoride-stimulation of adenylate cyclase activity. The prostaglandin synthetase inhibitors acetyl salicylic acid and indomethacin and the phospholipase A2 inhibitor quinacrine all abolished the increase in adenylate cyclase activity produced by delta 9-THC, suggesting the involvement of prostaglandins in this cannabinoid action.
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PMID:Possible role of prostaglandins in the effects of the cannabinoids on adenylate cyclase activity. 631 73

The effects of endogenous phospholipase A2 activation by melittin on components of the beta adrenoceptor linked adenylate cyclase system were examined in cultured cardiac cells. Exposure of cardiac cells for one hour to melittin concentrations ranging from 0.125 microgram/ml to 5.0 micrograms/ml induced a concentration dependent hydrolysis of radioactively labelled phospholipids and loss of lysophospholipids from the cell membrane. Melittin concentrations of 2.5 micrograms/ml or greater markedly attenuated the isoprenaline induced rise in cyclic AMP. In vitro studies using cell homogenates suggest that phospholipase A2 activation by the higher concentration of melittin (5 micrograms/ml) partially uncoupled the beta adrenoceptor from adenylate cyclase. Beta adrenoceptor number estimated by 125I-iodohydroxybenzylpindolol specific binding as well as the affinity of isoprenaline for these binding sites were unaffected by melittin pre-exposure. The percentage stimulation of adenylate cyclase by sodium fluoride or guanylylimidodi-phosphate was not significantly affected by activation of endogenous phospholipase A2. Phosphodiesterase activity in the soluble fraction of cell homogenates increased marginally (9%, P = 0.05) in cells exposed to melittin. These results suggest that activation of endogenous phospholipase A2 within the sarcolemma can modulate the activity of the beta adrenoceptor linked adenylate cyclase system of intact cardiac cells. The reduced beta adrenoceptor responsiveness of the cells appears to be primarily due to an alteration in coupling between the beta adrenoceptor and the guanine nucleotide binding protein components of the adenylate cyclase system and not between the latter and the catalytic subunit.
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PMID:The effects of endogenous phospholipase A2 activation on beta adrenoceptor function in cardiac cells. 631 71

Phospholipase A2 (PLA2) increases adenylate cyclase (AC) activity in the rat caudate nucleus in a dose-dependent manner. After maximal stimulation by fluoride, PLA2 treatment further increases AC activity 2.4 fold. Adenylate cyclase activity is maximal after 45% hydrolysis of the phospholipids. Of the products of PLA2 treatment only lysophosphatidylcholine (LPC) produces such an increase in AC activity. In contrast to PLA2 treatment, LPC solubilizes the enzyme, decreases the Km value for ATP, and requires much larger amounts of LPC than that produced by lipase treatment. After maximal stimulation with fluoride and PLA2, removal of most of the LPC does not reduce the activity of adenylate cyclase. These findings suggest that removal of membrane lipid rather than generation of LPC is responsible for the activation of brain adenylate cyclase by phospholipase A2.
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PMID:Activation of fluoride-stimulated adenylate cyclase by phospholipase A2 in the caudate nucleus of the rat brain. 662 79

The ejaculated porcine spermatozoa were fractionated into the cytosol, membrane, midpiece plus tail (flagella) and head fractions, and their adenylate cyclase activities were measured. About 65% of the total activity was located in the flagella fraction. For all the fractions, Mn2+-dependent adenylate cyclase activity was about 20 times higher than Mg2+-dependent activity, and guanine nucleotides, fluoride, and other reagents tested did not activate adenylate cyclase. The results suggest that the GTP-dependent regulatory subunit is absent in porcine spermatozoa. The porcine seminal plasma was found to stimulate the adenylate cyclase activity in spermatozoa. The stimulating factor in porcine seminal plasma was partially purified by gel filtration and the molecular weight of the factor appeared to be between 200 and 300. The partially purified factor is heat stable and is not inactivated by treatment with Pronase, trypsin, phospholipase A2 or D but is inactivated by acid hydrolysis. It is easily soluble in water, partially soluble in methanol, and insoluble in ethanol, ethyl ether, chloroform, or acetone. The activation of sperm adenylate cyclase by the factor occurred without a time lag. The activating effect was dose-dependent, saturated at high dose, and ascribed to the increase of the maximal velocity (Vmax). The effect of the factor appears to be limited to adenylate cyclase in spermatozoa; the factor activated adenylate cyclase both in porcine and bovine spermatozoa but failed to activate those in other porcine tissues. The factor was shown to activate the enzyme not only in the ejaculated spermatozoa but also in the epididymal sperm. The factor was also found to elevate the cAMP level in the intact porcine spermatozoa. The factor enhanced the motility of corpus and cauda epididymal spermatozoa. These findings indicate the possibility that this factor initiates the spermatozoan motility upon ejaculation through directly activating adenylate cyclase.
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PMID:Activation of spermatozoan adenylate cyclase by a low molecular weight factor in porcine seminal plasma. 663 Feb 19

1. The effect of various proteolytic enzymes was assayed on the adenylate cyclase activity in purified brain membrane preparations from the insect Ceratitis capitata. Trypsin, chymotrypsin, papain, thermolysin, elastase, subtilisin and prot. XIV were examined. 2. Trypsin treatment, at 37 degrees C, decreased the adenylate cyclase activity even in the presence of GppNHp that protects the activity from the thermal inactivation. 3. Residual basal, GppNHp- and F(-)-stimulated activities were similar when membrane preparations were preincubated either in the presence or in the absence of GppNHp and F-. 4. All proteolytic activities assayed on the brain membrane preparations, excepting papain, exerted an inhibition of adenylate cyclase in basal conditions. 5. The inhibition was stronger in the presence of F- than in the presence of other regulators. 6. Papain showed also a notable inhibition of adenylate cyclase in the presence of F-. 7. Phospholipase A2 treatment decreased both basal and stimulated activity; however, F(-)-sensitive activity was less affected than basal and GppNHp-sensitive activity. F(-)-stimulated activity was less affected by phospholipase A2 than either basal or GppNHp-stimulated activities. 8. Phospholipids are, then, essential for the highest basal activity, although the relationship between catalytic and nucleotide-regulatory components was unaffected by this treatment.
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PMID:Effect of proteolytic and lipolytic enzymes on the adenylate cyclase activity from brain membranes of Ceratitis capitata. 675 15

Convulxin (Cx), a component of the venom of the snake Crotalus durissus cascavella, induced the concentration-dependent aggregation of guinea-pig platelets when used at and above 50 +/- 5 ng/ml, accompanied by the release of ATP and by the formation of thromboxanes (Tx). Platelet activation by Cx was not due to potential contaminants found in the crude snake venom, such as phospholipase A2 and clotting enzymes. Aspirin (50-100 microM) failed to interfere with the platelet effects of Cx, demonstrating independence from cyclo-oxygenase. In contrast, indomethacin (50 microM) displayed a distinct inhibitory activity on the effects of Cx, as compared to aspirin, and thus exerts cyclo-oxygenase-independent effects on platelet activation. The ADP scavenger creatine phosphate/creatine phosphokinase (CP/CPK) inhibited aggregation by Cx used at concentrations below 6-8 times the threshold, but failed to interfere with higher amounts. Platelet aggregation by Cx was inhibited and reversed once established by EDTA (5mM) and by prostacyclin (0.1-1 microM). Cx-induced activation of platelets is thus Ca2+-dependent and liable to control by the adenylate cyclase-cyclic AMP system. Convulxin induced hypotension, bronchoconstriction and thrombocytopenia when injected i.v. to the anesthetised guinea pig at 0.3-3 microgram/kg. Aspirin and indomethacin (20 and 5 mg/kg respectively) mepyramine and methysergide (02. mg/kg) failed to interfere with these effects, but the combination of either aspirin or indomethacin with methysergide and mepyramine, suppressed the bronchial effects of Cx, leaving the hypotensive and thrombopenic effects unchanged. This synergism remains unexplained. Bronchoconstriction was platelet-dependent, being suppressed by platelet depletion with antiplatelet serum or by i.v. prostacyclin (1-10 microgram/kg).
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PMID:Activation of guinea-pig platelets induced by convulxin, a substance extracted from the venom of Crotalus durissus cascavella. 700 69

Integrated chorda tympani (CT) recordings were made to salty, sour, sweet, bitter, and glutamate tastants before and after a 4-min application of modulators of lipid-derived second messenger systems. The modulators included two membrane-permeable analogues of DAG, 1-oleoyl-2-acetyl glycerol (OAG) and dioctanoyl glycerol (DiC8); thapsigargin, which releases Ca++ from intracellular stores; ionomycin, a calcium ionophore; lanthanum chloride, an inorganic calcium channel blocker; nifedipine, a dihydropyridine calcium channel blocker; quinacrine diHCl, a phospholipase A2 antagonist; melittin, a phospholipase A2 agonist; and indomethacin, which decreases the release of prostaglandins by inhibiting the enzyme cyclo-oxygenase. The main findings were: OAG (125 microM) and DiC8 (100 microM) blocked the responses of several bitter compounds while enhancing the taste response to several sweeteners. Lanthanum chloride blocked all responses, which may be due to the fact that it blocks tight junctions. Quinacrine (1 mM) suppressed several bitter responses while enhancing the response to several sweeteners. The enhancement of sweet taste responses by DAG analogues suggests that there is cross-talk between the adenylate cyclase system and one (or more) pathways involving lipid-derived second messengers in taste cells.
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PMID:Effect of lipid-derived second messengers on electrophysiological taste responses in the gerbil. 750 78


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