OBSERVATIONS ON THE VACUOLOGENIC ACTIVITY OF NICOTINE IN MACROPHAGES

¹ Department of Pharmacology, Georgetown University Schools of Medicine and Dentistry, Washington, D.C.

Incubation of mouse peritoneal macrophages with nicotine tartrate resulted in the vaculation of the cells. The vacuologenic activity of nicotine was dose-and time-related; high concentrations (e.g., >2.87 mM) were active within 30 minutes, whereas lower concentrations (e.g., 0.29 mM) required 24 hours for vacuologenic activity. All of the nicotille-induced vacuolation was reversible within 15 to 30 minutes after return of the cells to nicotine-free medium. In studies with isotopically labeled nicotine, the loss of radioactivity from the cells corresponded in time frame with the loss of vacuolation. Both the ability of nicotine to induce a rapid vacuolation and the rapid reversibility of this vacuolation pointed to a mechanism other than energy-dependent pinocytosis for the changes observed. Nicotine was demonstrated to have a surfactant activity which might play a part in the mechanism of vacuologenesis. It is felt that this type of activity is closely related to the membrane stabilizing effect of amines on crythrocytes. The vacuologenic activity of nicotine, regardless of its mechanism, may be useful in explaining previous observations which indicated that nicotine blocked pinocytosis and increased exoeytosis by macrophages.