Mode of Action of Lithium on the Catalytic Unit of Adenylate Cyclase from Rat Brain

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Abstract
The action of lithium on calcium‐calmodulin‐activated and forskolin‐activated catalytic unit of adenylate cyclase has been studied. The catalytic unit was solubilized from rat brain and separated from the guanine nucleotide binding protein by gel filtration. Calcium‐calmodulin‐stimulated and forskolin‐stimulated catalytic unit activities were inhibited in the presence of 2 mM and 1 mM of lithium, respectively. No inhibitory effect was observed on the basal activity. The inhibitory effect of lithium on the stimulated activities was antagonized by magnesium. Lithium did not influence the interaction of the enzyme substrate (ATP) with the catalytic unit. The present results indicate that lithium interacts directly with the catalytic unit of the adenylate cyclase system. In the neuron, lithium might interfere with a divalent cation site on the catalytic unit.

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