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Isoquinoline alkaloids

Inhibitory actions on cation-dependent ATP-phosphohydrolases

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Abstract

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 nonlinear competitive inhibition with respect to Na+-activation. Additionally, these alkaloids significantly inhibit rat brain microsomal K+-activatedpNPPase. The results demonstrate that certain members of several classes of isoquinoline alkaloids markedly affect various cation-dependent phosphohydrolases in vitro.

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Authors and Affiliations

  1. Neurochemistry and Addiction Research Laboratory, Veterans Administration Hospital, 77211, Houston, Texas

    Laurence R. Meyerson, Kenneth D. McMurtrey & Virginia E. Davis

  2. Departments of Medicine and Biochemistry, Baylor College of Medicine, Houston, Texas

    Laurence R. Meyerson, Kenneth D. McMurtrey & Virginia E. Davis

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Meyerson, L.R., McMurtrey, K.D. & Davis, V.E. Isoquinoline alkaloids. Neurochem Res 3, 239–257 (1978). https://doi.org/10.1007/BF00964063

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