Cyclic AMP metabolism in brain.

A method for measuring the rate of production of C-labelled 14 adenine nucleotides from C-ATP was developed and used to study the relationship of adenyl cyclase to other membrane-bound ATP utilizing enzymes and cyclic 3', 5'-nucleotide phosphodiesterase (PDE) in preparations of rat cerebral cortex and guinea-pig pancreas. It was shown that NaF and Mn++ increased cyclic AMP accumulation in these preparations, in part, by an inhibition of PDE activity. Adrenaline and ouabain stimulated cyclic AMP accumulation by a method not related to inhibition of other membrane-bound ATP utilizing enzymes or to inhibition of PDE activity. Adrenaline stimulation of cyclic AMP accumulation in the synaptic membrane preparation required the presence of Ca++ in the preparation media. Inhibition of a soluble PDE preparation from rat cerebral cortex was maximal in the presence of ATP and ADP and much lower in the presence of methylene analogs of ATP