Effect of replacement of extracellular sodium ions and of D-600 on the activation by adrenalin of adenylate cyclase in intact pigeon erythrocytes

The effect of replacement of extracellular Na⁺ by Li⁺, choline, K⁺ or sucrose on cyclic AMP formation in pigeon erythrocytes has been investigated. Replacement of extracellular Na⁺ by Li⁺, choline or sucrose but not by K⁺ inhibited the stimulation by adrenalin of cyclic AMP formation, but had no detectable effect on cyclic AMP content in the absence of adrenalin. This inhibition was observed in the presence or absence of extracellular Ca²⁺. The relative inhibition caused by Na⁺ removal decreased with increasing adrenalin concentration. It was concluded that extracellular Na⁺ or K⁺ ions were required for maximal activation of adenylate cyclase by low concentrations of adrenalin, and that this effect of monovalent cations may have been due to an effect on the affinity of the receptor for adrenalin.The verapamil derivative D-600 also inhibited the stimulation by adrenalin of cyclic AMP formation. This effect occurred in the absence of extracellular Ca²⁺ and hence seemed to be unrelated to the inhibition by D-600 of the slow Ca²⁺ channel in electrically excitable tissues.