Effect of metal chelating agents on the storage of norepinephrine in vitro by cerebral synaptic vesicles

Autor: R. D. Wiehle, R. W. Colburn, John M. Davis, W. H. Riesen, K. S. Rajan
Rok vydání: 1977
Předmět:
Zdroj: Biochemical Pharmacology. 26:1703-1708
ISSN: 0006-2952
Popis: The inhibitory effects of fourteen different metal chelating agents on the storage in vitro of [ 3 H] dl -norepinephrine (NE) by the isolated synaptic vesicles from rat brain were investigated with a view to explore the possible importance of metal chelation phenomena. The chelators under examination belong to the classes of polyamines, aminocarboxylic and hydroxy carboxylic acids exhibiting a wide range of metal-binding strengths. Values of ic 50 , viz., the amount of the chelator which will inhibit 50 per cent of the storage of [ 3 H] dl -NE, were determined for the different compounds. The strengths of chelate formation of the “synaptosomal and vesicular metal ions”, viz. Cu 2+ , Fe 2+ , Fe 3+ , Zn 2+ , Mg 2+ and Ca 2+ , with the above compounds were compared with their inhibition in vitro of the vesicular storage of [ 3 H] dl -NE in order to determine if a correlation existed between the two. On the basis of regression analyses of the data on the stabilities of the individual metal chelates (log K ML ) and the inhibitory effects of the different chelators (log ic 50 /NE), significant correlation coefficients were obtained with the Cu 2+ and Zn 2+ amine systems, i.e. 0.98 with P 2+ gave the most satisfactory correlation coefficient, i.e. 0.91, P
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