Effect of Acetylcholine on Rate of Uptake and Equilibrium Distribution of Physostigmine in Human Erythrocytes

¹ From the Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee

Incubation of human erythrocytes with physostigmine sulfate results in a rapid uptake of the cationic alkaloid by red cells. The reaction is essentially complete at the end of 1 hour. At equilibrium the drug is concentrated in the biophase by a factor of 1.5–10.0, depending on the concentration of the drug. Acetylcholine in a concentration range of 10^–2–10^–4m depresses the rate of binding and diminishes the equilibrium distribution ratio of the compound, the maximal effect of acetylcholine being reached at a concentration of 10^–2m. From the data obtained, estimates were made of the extent to which the acetylcholine-cholinesterase system could contribute to ion transport processes in mammalian erythrocytes. From the analysis, it would appear that if cholinesterase plays a role in cation transport (Na and K), it could affect the transport rate of only a small fraction of the total cell cations, (less than 10^–5 mole/l. of cells). The hypothesis that the physostigmine cation, as well as cations in general, enter erythrocytes through two different ‘pores’ or ‘channels’ in the cell membrane is presented and discussed. Possible application of this idea to ion transport processes in other tissues is considered.