Effects of local anaesthetics on intracellular fusion processes. Enhancement of concanavalin A-induced macrophage vacuolation.
The extensive vacuolation elecited in mouse peritoneal macrophages in response to interaction with concanavalin A is markedly enhanced by a simultaneous exposure to anaesthetics. The potency of enchancing vacuolation increases within the series of normal alcohols with chain length C10 greater than C8 greater than C7 greater than C6. From the four tertiary amine local anaesthetics tested lidocaine and procaine are by far more effective than tetracaine and dibucaine. The latter two induce extensive cell shrinkage at concentrations at which the first two exhibit optimum enhancing capacity. Of the tested compounds chlorpromazine has the highest membrane/buffer partition coefficient and it exhibits its optimum enhancing effect on concanavalin A-induced macrophage vacuolation at the lowest drug concentration. The binding of [3H] concanavalin  A as well as its internalization by macrophages incubated with the lectin for 15, 45 and 90 min are not affected significantly in the presence of decanol, procaine or chlorpromazine at concentrations of maximum enhancing effect on vacuolation. Thus enhancement of vacuolation does not stem from an increase in the rate or extent of concanavalin A interiorization. The rate at which vacuoles are generated is however markedly increased in the presence of chlorpromazine and the resulting vacuoles are of a larger diameter. At 2-5 fold the concentration required for inhibition of maximum enhancing effect, the drugs lead to extensive macrophage shrinkage and to depletion of intracellular ATP. Phagocytosis of heat-killed yeast cells is reduced by tertiary amine anaesthetics at concentrations optimal for enhancement of concanavalin A-induced vacuolation. Enhanced intracellular fusion of concanavalin A-bearing pinosomes to form vacuoles is discussed in terms of current ideas on factors vacuoles is discussed in terms of current ideas on factors vacuoles is discussed in terms of current ideas on factors affecting membrane fusion and the effects of anaesthetics on membrane organization of lipids, intramembraneous particles, glycoprotein receptors and the possible control by cytoskeletal elements. The results best fit the hypothesis that enhanced fusion correlates with membrane aggregation of both intramembraneous particles and concanavalin A receptor and the formation of areas relatively deplete of these structures and enriched in phospholipids.
D000255:Adenosine Triphosphate / Q000378:metabolism; D000779:Anesthetics, Local / Q000494:pharmacology*; D000818:Animals; D001665:Binding Sites; D002746:Chlorpromazine / Q000494:pharmacology; D003208:Concanavalin A / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008856:Microscopy, Fluorescence; D009940:Organoids / Q000502:physiology*; D010587:Phagocytosis / Q000187:drug effects; D012440:Saccharomyces; D014617:Vacuoles / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure
D000779:Anesthetics, Local; D003208:Concanavalin A; D000255:Adenosine Triphosphate; D002746:Chlorpromazine