Abstract
Histamine and epinephrine stimulate the activity of guinea pig heart adenylate cyclase [ATP pyrophosphate-lyase (cyclizing) EC 4.6.1.1], in part, by decreasing the requirement for Mg2+ as an activator. This effect may represent an increase in affinity for Mg2+ and/or a decrease in sensitivity of the enzyme towards inhibition by free ATP. Both of these inotropic hormones increase Vmax. Pretreatment of the membrane-bound enzyme with EDTA, to remove available divalent cations, almost eliminates persistent stimulation by guanyl-5''-yl imidodiphosphate [Gpp(NH)p]. Addition of Mg2+ to the preincubation medium restores the capacity of Gpp(NH)p to acutely activate the enzyme. Mg2+ probably interacts with the nucleotide (GTP) regulatory site. Persistent stimulation of the enzyme by Gpp(NH)p or F- also involves a decrease in the requirement for Mg2+ and an increase in Vmax.