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

Representatives of eleven different classes of isoquinoline alkaloids inhibit Na+, K+-ATPase and Mg2+-ATPase in rat brain microsomal preparations. In most cases the Na+, K+-ATPase is more sensitive than Mg2+-ATPase to inhibition by the alkaloids. The classes of alkaloids can be ranked according to potency of inhibition of Na+, K+-ATPase. Protoberberines are most effective, followed in decreasing order by benzophenanthridines, benzylisoquinolines, aporphines, tetrahydroprotoberberines, pavines, protopines, isoquinolines, tetrahydrobenzylisoquinolines, morphinanes, and tetrahydroisoquinolines. As specific representatives of each of the first four classes of alkaloids, berberine, sanguinarine, papaveroline and 1,2,10,11-tetrahydroxyaporphine, respectively, prove most valuable in kinetic studies because they exhibit the greatest inhibitory action on brain Na+, K+-ATPase. Kinetic analyses plotted in double reciprocal form reveal that berberine and 1,2,10,11-tetrahydroxyaporphine are simple linear competitive inhibitors with respect to ATP, whereas sanguinarine and papaveroline are simple linear noncompetitive inhibitors. These four representative alkaloids exhibit non-linear competitive inhibition with respect to Na+-activation. Additionally, these alkaloids significantly inhibit rat brain microsomal K+-activated pNPPase. The results demonstrate that certain members of several classes of isoquinoline alkaloids markedly affect various cation-dependent phosphohydrolases in vitro.
 ...
PMID:Isoquinoline alkaloids. Inhibitory actions on cation-dependent ATP-phosphohydrolases. 14 28

6,7-Dimethoxy-1-(3,4-dimethoxybenzyl)-4-([4-(2-methoxyphenyl)-1- piperazinyl]methyl)isoquinoline (Ro 22-4839) is a new cerebral circulation improver with vasospasmolytic properties. Preliminarily, Ro 22-4839-induced arterial relaxation was confirmed under the treatment of various constrictors and it was hardly overcome by addition of extra calcium. In this study the mode and site of action of this agent were further explored. Ro 22-4839 was found to more strongly inhibit the superprecipitation of chicken gizzard smooth muscle actomyosin (IC50 = 2.0 mumol/l) than trifluoperazine (38 mumol/l) and W-7 (N-(6-aminohexyl)-5-chloro-1-naphthalene-sulfonamide) (220 mumol/l), an in vitro model for relaxation-contraction coupling of the smooth muscle in which calmodulin is known to play an important role through phosphorylation of myosin light chain kinase. The calmodulin antagonistic action of Ro 22-4839 was also demonstrated in other calmodulin-related reaction systems such as phosphodiesterase and hydrophobic fluorescent probe, but was very weak in Ca2+, Mg2+-ATPase of rat erythrocyte membrane. Thus, Ro 22-4839 was suggested to have a relative preference for smooth muscle contraction process unlike trifluoperazine and W-7. Moreover, Ro 22-4839 prevented the decrease in erythrocyte deformability induced by hyperosmolarity or intracellular Ca2+ accumulation, like trifluoperazine and W-7. However, Ro 22-4839 itself caused hardly an internal stomatocytic shape of erythrocytes in contrast to known calmodulin antagonists. Further, Ro 22-4839 inhibited erythrocyte membrane rupture, platelet aggregation and lipid peroxidation.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Calmodulin antagonistic action of the cerebral circulation improver 6,7-dimethoxy-1-(3,4-dimethoxybenzyl)-4- ([4-(2-methoxyphenyl)-1-piperazinyl]methyl)isoquinoline. 282 56

Papaverine (1-[(3,4-Dimethoxyphenyl) methyl]-6,7-dimethoxyisoquinoline) and nantenine (O-methyldomesticine) are chemically related isoquinoline alkaloids displaying similar dose-dependent sedative or convulsant effects, but seem to act differentially on synaptosomal membrane enzymes. Na+, K+-, Mg2+- and Ca2+-ATPase activities were inhibited by nantenine but not by papaverine, whereas acetylcholinesterase activity remained unchanged by nantenine but slightly enhanced by papaverine. Nantenine inhibited roughly both 20-50% Ca2+- and Mg2+-ATPase activities but 40-90% Na+, K+-ATPase activity. Kinetic analysis indicated that nantenine interacts with the substrate ATP for Ca2+-ATPase activity but that it competes with K+ for Na+, K+-ATPase activity. Given the roles of Na+, K+-ATPase and Ca2+-ATPase in cation transport and [Ca2+]i regulation, respectively, the inhibitory effect of nantenine upon these enzymes may explain its convulsant effect though not its sedative activity. The sedative action of both nantenine and papaverine is hardly attributable to an effect on the synaptosomal membrane enzymes assayed.
 ...
PMID:Nantenine and papaverine differentially modify synaptosomal membrane enzymes. 1096 26