Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.6.3.1 (Mg2+-ATPase)
 1,484 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The relationship between adenylate cyclase activity in the synaptic membrane fraction (M1) of rat brain and lipid peroxidation of these membranes was examined. In the presence of 5 mM dithiothreitol (DTT), 1 to 10 microM Fe/+ activated adenylate cyclase 2- to 4-fold. Of several metal ions, Fe2+ was the most effective. Other enzymes in M1, such as Mg2+-ATPase, (Na+-K+)-ATPase, 5'-nucleotidase, acetylcholinesterase, and phosphodiesterase, were not activated by Fe2+ plus DTT. Activation of adenylate cyclase by Fe2+ plus DTT was accompanied by production of malondialdehyde, a product of lipid peroxidation. Formation of malondialdehyde was completely parallel with enzyme activation. Ascorbic acid or a NADPH system also stimulated enzyme activity and caused lipid peroxidation. Activation of the enzyme and lipid peroxidation induced by Fe2+ plus DTT, ascorbic acid, or NADPH was completely prevented by simultaneous addition of N,N'-diphenyl-p-phenylenediamine, an inhibitor of lipid peroxidation. This inhibitor also prevented the decrease in turbidity of the enzyme preparation induced by Fe2+ plus DTT. The stimulatory effects of NaF, guanylyl-5'-imidodiphosphate and calmodulin, respectively, and that of Fe2+ plus DTT on the enzyme activity were additive. Activation of adenylate cyclase by Fe2+ plus DTT was only observed in brain synaptic membranes, not in erythrocyte ghosts, liver plasma membranes, or cardiac sarcolemma. These results indicate that lipid peroxidation of synaptic membranes was accompanied by specific stimulation of adenylate cyclase activity.
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PMID:Activation of adenylate cyclase of rat brain by lipid peroxidation. 721 51

1. Stellettamide A (ST-A), a novel marine toxin isolated from a marine sponge, inhibited high K+(72.7 mM)-induced contraction in the smooth muscle of guinea-pig taenia coli with an IC50 of 88 microM. 2. In the taenia permeabilized with Triton X-100, ST-A inhibited Ca2+ (3 and 10 microM)-induced contractions with an IC50 of 46 microM for 3 microM Ca2+ and 105 microM for 10 microM Ca2+. In the permeabilized taenia, calyculin-A (300 nM), a potent inhibitor of type-1 and type-2A phosphatases, induced sustained contraction in the absence of Ca2+. ST-A had no effect on this contraction. 3. ST-A inhibited Mg2+-ATPase activity in native actomyosin prepared from chicken gizzard with an IC50 of 25 microM. 4. In a reconstituted smooth muscle contractile system containing calmodulin, myosin light chain (MLC) and MLC kinase, ST-A inhibited MLC phosphorylation with an IC50 of 152 microM. The inhibitory effect of ST-A was antagonized by increasing the concentration of calmodulin. 5. ST-A inhibited calmodulin activity, assessed by Ca2+/calmodulin-dependent enzymes, (Ca2+-Mg2+)-ATPase of erythrocyte membrane, with an IC50 of 100 microM and phosphodiesterase prepared from bovine cardiac muscle with an IC50 of 52 microM. The inhibitory effect on phosphodiesterase activity was antagonized by increasing the calmodulin concentration. 6. Interaction between ST-A and calmodulin was demonstrated by instantaneous quenching of the intrinsic tyrosine fluorescence of calmodulin by ST-A (3-300 microM). Similar results were obtained in the presence or absence of Ca2+ suggesting that ST-A binds to calmodulin and that Ca2+ is not essential for the binding of ST-A to calmodulin. 7. These results suggest that ST-A, isolated from marine metabolites, is a novel inhibitor of calmodulin.
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PMID:Stellettamide-A, a novel inhibitor of calmodulin, isolated from a marine sponge. 925 8

In vitro and ex vivo interactions of betaadrenoceptor blocking drugs, antihistamines and chloroquine with blood platelets and polymorphonuclear leukocytes resulted in different alterations of regulatory functions of these blood cells. Inhibition of platelet aggregation, arachidonate regulatory pathway, 5-hydroxytryptamine transportation, removal of platelet membrane receptors, inhibition of second messenger pathways at subcellular level and suppression of phagocytosis are indicative of nonreceptor rather than specific receptor interactions. Binding of drugs with biomembranes is reversible depending on the ionic charge of the molecule and hydrophobicity of the bilayer, partition coefficient, pH and pKa of the amphiphilic molecules and other physico-chemical properties of amphiphilic drugs. Alterations in the drug molecule structure alters the drug-phospholipid binding profile. Any change in the metabolism of membrane phospholipids directly or indirectly influences one or more of the important components of the phospholipid-signalling pathway. In addition to changes in phospholipase A, C and D activities, protein kinase C, calmodulin-phosphodiesterase, Ca2+,Mg2+-ATPase, Na+,K+-ATPase and other messengers were found to be changed in cells and tissue after cationic amphiphilic drug (CAD) administration. Although not much has been understood of the mechanism by which some CAD affect immune functions, there are good reasons to suggest that these effects might occur. CADs share sufficient similarities in their structure even though they come from diverse pharmacological classes. CADs affect ion transport, immune functions, tumour growth, serotonin metabolism and several other functions in the body. Extensive therapeutic use and associated side effects have generated a great deal of interest in understanding the nonreceptor interactions with CADs.
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PMID:Antiplatelet and antileukocyte effects of cardiovascular, immunomodulatory and chemotherapeutic drugs. 1684 9


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