Guanine nucleotides protect adenylate cyclase against inhibition by Pb2+

The inhibition of rat liver adenylate cyclase (ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1) by Pb2+ could be separated into an irreversible and a reversible component. Evidence was obtained that both types of inhibition were due to free Pb2+, rather than Pb/ATP, and that Pb2+ did not act via the site wherein Mg2+ and Mn2+ activate the cyclase. Guanine nucleotides strongly counteracted the reversible inhibition of cyclase by Pb2+, providing another example of guanine nucleotide effects on adenylate cyclase function. It is suggested that the Pb2+-inhibited cyclase may be of value in the study of guanine nucleotide-cyclase interactions.