Molecular Pharmacology, Vol 12, 390-398, Copyright © 1976 by the American Society for Pharmacology and Experimental Therapeutics

Heavy Metals and Adenosine Cyclic 3',5'-Monophosphate Metabolism: Possible Relevance to Heavy Metal Toxicity

¹ Laboratory of Neuropharmacology, St. Elizabeths Hospital, National Institute of Mental Health, Washington D. C. 20032

Adenylate cyclase activity in homogenates and particulate fractions of rat cerebellum, cerebral cortex, salivary gland, heart, and liver was inhibited by very low concentrations of lead ions (I₅₀ < 3 µM). Both basal and hormone-stimulated activities were affected, and the inhibition was not dependent upon calcium or ATP concentration. Inhibition was reversed by 2-mercaptoethanol but not by ethylene glycol bis (-aminoethyl ether)-N,N'-tetraacetic acid.) Very low concentrations (I₅₀ = 1-8 µM) of zinc, copper, cadmium, mercury, uranium, silver, and gold ions also inhibited adenylate cyclase. Cyclic AMP phosphodiesterase activity was inhibited by these same heavy metals, with the exception of lead, which stimulated phosphodiesterase. The nonheavy metals aluminum, iron, and nickel had little effect on either enzyme. These effects of heavy metals in vitro raise the possibility that alteration of cyclic AMP metabolism, together with other membrane effects, may underlie some of the toxic signs present in certain types of heavy metal poisoning.

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