Effects of dibucaine on the endocytic/exocytic pathways in Trypanosoma cruzi.
Although local anesthetics (LA) are considered primarily Na+-channel blockers in the past decade, an alternative action of LA as inhibitors of fusion among compartments of the endocytic/exocytic pathways was described. In epimastigote forms of Trypanosoma cruzi, we observed that 50 mM dibucaine reduced the rates of uptake of bovine serum albumin (BSA) and immunoglobulin to 60% of control values in addition to the delay of exocytosis of cysteine proteases. Fusion among endocytic compartments was not inhibited in the presence of dibucaine because previously labeled reservosomes was loaded with a second label in sequential pulse-chase experiments. However, dibucaine reduced the degradation of BSA-gold complex in the reservosomes, which was not caused either by an inhibition of the whole proteolytic activity of the parasite or by a reduction on the expression levels of cruzipain. The immunocytochemical analysis suggested that the inhibition of the degradation of gold-labeled BSA in reservosomes could be due to a subversion of the regular traffic of proteases toward the reservosomes in dibucaine-treated cells.
Souto-Padrón
Thaïs
T
Instituto de Microbiologia Prof. Paulo de Góes, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil. souto.padron@micro.ufrj.br
Lima
Ana Paula
AP
Ribeiro
Rachel de Oliveira
Rde O
D000779:Anesthetics, Local / Q000494:pharmacology*; D000818:Animals; D002451:Cell Compartmentation / Q000187:drug effects; D003546:Cysteine Endopeptidases / Q000378:metabolism; D003992:Dibucaine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004705:Endocytosis / Q000187:drug effects*; D005089:Exocytosis / Q000187:drug effects*; D007136:Immunoglobulins / Q000378:metabolism; D012710:Serum Albumin, Bovine / Q000378:metabolism; D014349:Trypanosoma cruzi / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure
D000779:Anesthetics, Local; D007136:Immunoglobulins; D012710:Serum Albumin, Bovine; D003546:Cysteine Endopeptidases; D003992:Dibucaine