Skip to main content
Log in

Effects of dibucaine on the endocytic/exocytic pathways in Trypanosoma cruzi

  • Review
  • Published:
Parasitology Research Aims and scope Submit manuscript

Abstract

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  • Balboa MA, Sáez Y, Balsinde J (2003) Calcium-independent phospholipase A2 is required for lysosyme secretion in U937 promonocytes. J Immunol 170:5276–5280

    PubMed  CAS  Google Scholar 

  • Bogitsh BJ, Ribeiro-Rodrigues R, Carter CE (1996) A ultrastructure study study of the in vitro effects of L-leucin methyl ester and ammonium chloride on Trypanosoma cruzi epimastigotes. Parasitol Res 82(4):285–290

    Article  PubMed  CAS  Google Scholar 

  • Cappai RA, Osborn H, Gleeson PA, Handman E (1993) Cloning and characterization of a Golgi-associated GTP-binding protein homologue from Leishmania major. Mol Biochem Parasitol 62:73–82

    Article  PubMed  CAS  Google Scholar 

  • Clayton C, Hausler T, Blattner J (1995) Protein trafficking in kinetoplastid protozoa. Microbiol Rev 59:325–344

    PubMed  CAS  Google Scholar 

  • Coppens I, Opperdoes F, Courtoy PJ, Baldhuin P (1987) Receptor mediated endocytosis in the bloodstream form of Trypanosoma brucei. J Protozool 34:465–473

    PubMed  CAS  Google Scholar 

  • Coppens I, Bastin P, Opperdoes F, Baldhuin P, Courtoy PJ (1992) Trypanosoma brucei brucei: antigenic stability of LDL receptor of the mammalian host. Exp Parasitol 74:77–86

    Article  PubMed  CAS  Google Scholar 

  • De Figueiredo P, Drecjtrah D, Katzenellenbogen JA, Strang M, Brown WJ (1998) Evidence that phospholipase A2 acativity is required for Golgi complex and trans Golgi network membrane tubulation. Proc Natl Acad Sci U S A 95:8642–8647

    Article  PubMed  Google Scholar 

  • De Figueiredo P, Drecjtrah D, Polizotto RS, Cole NB, Lippincott-Schwartz J, Brown WJ (2000) Phospholipase A2 antagonists inhibited constitutive retrograde membrane traffic to the endoplasmic reticulum. Traffic 1:504–511

    Article  PubMed  Google Scholar 

  • De Souza W, Carvalho TU, Benchimol M (1978) Trypanosoma cruzi: ultrastructural, cytochemical and freeze-fracture studies of protein uptake. Exp Parasitol 45:101–115

    Article  PubMed  Google Scholar 

  • Eakin AE, Miles AA, Harth G, McKerrow JH, Craik CS (1992) The sequence, organization and expression of the major cysteine protease (cruzipain) from Trypanosoma cruzi. J Biol Chem 267:7411–7420

    PubMed  CAS  Google Scholar 

  • Engel JC, Doyle PS, Palmer J, Hsieh I, Bainton DF, McKerrow JH (1998) Cysteine protease inhibitors alter Golgi complex ultrastructure and function in Trypanosoma cruzi. J Cell Sci 111:597–606

    PubMed  CAS  Google Scholar 

  • Engstler M, Thilo L, Weise F, Grünfelder CG, Schwartz H, Boshart M, Overath P (2004). Kinetics of endocytosis and recycling of the GPI-anchored variant surface glycoprotein in Trypanosoma brucei. J Cell Sci 117:1105–1115

    Article  PubMed  CAS  Google Scholar 

  • Field H, Farjah M, Pal A, Gull K, Field MC (1998) Complexity of trypanosomal endocytosis pathway revealed by Rab4 and Rab5 isoforms in Trypanosoma brucei. J Biol Chem 27:32102–32110

    Article  Google Scholar 

  • Figueiredo RCBQ, Soares MJ (2000) Low temperature blocks fluid-phase pinocytosis and receptor–mediated endocytosis in Trypanosoma cruzi epimastigotes. Parasitol Res 86:413–418

    Article  PubMed  Google Scholar 

  • Ghedin E, Debrabant A, Engel JC, Dwyer DM (2001) Secretory and endocytic pathways converge in a dynamic endosomal system in a primitive protozoan. Traffic 2:175–188

    Article  PubMed  CAS  Google Scholar 

  • Hagiwara Y, Ozawa E (1990) Suppression of transferrin internalisation in myogenic L6 cells by dibucaine. Biochim Biophys Acta 1051:237–241

    Article  PubMed  CAS  Google Scholar 

  • Hollmann MW, Wieczorek KS, Berger A, Durieux ME (2001) Local anesthetic inhibition of G protein-coupled receptor signaling by interference with Gαq protein function. Mol Pharmacol 59:294–301

    PubMed  CAS  Google Scholar 

  • Jeffries TR, Morgan GW, Field MC (2001) A developmentally regulated Rab11 homologue in Trypanosoma brucei is involved in recycling processes. J Cell Sci 114:2617–2626

    PubMed  CAS  Google Scholar 

  • Langreth SG, Balber AE (1975) Protein uptake and digestion is bloodstream and culture forms of Trypanosoma brucei. J Protozool 22:40–53

    PubMed  CAS  Google Scholar 

  • Lennartz MR, Yuen AFC, Masi SM, Russel DG, Buttle KF, Smith JJ (1997) Phospholopase A2 inhibition results in sequestration of plasma membrane into electronlucent vesicles during IgG-mediated phagocytosis. J Cell Sci 110:2041–2052

    PubMed  CAS  Google Scholar 

  • McConville MJ, Mullin KA, Ilgoutz SC, Teasdale RD (2002) Secretory pathway of trypanosomatid parasites. Microbiol Mol Biol Rev 66:122–154

    Article  PubMed  CAS  Google Scholar 

  • Mayorga LS, Colombo MI, Lennartz M, Brown EJ, Arman KH, Weiss R, Lennon PJ, Stahl PD (1993) Inhibition of endosome fusion by phospholipase A2 (PLA2) inhibitors points to a role for PLA2 in endocytosis. Proc Natl Acad Sci U S A 90:10255–10259

    Article  PubMed  CAS  Google Scholar 

  • Mendonça SM, Campos CBL, Gueiros-Filho FJ, Lopes UG (1993) Identification of GTPase genes in the protozoa parasites Trypanosoma cruzi and Leishmania amazonensis. Biol Res 26:3–9

    PubMed  Google Scholar 

  • Mendonça SM, Silva JLN, Cunha-e-Silva N, De Souza W, Lopes UG (2000) Characterization of Rab11 homologue in Trypanosoma cruzi. Gene 243:179–185

    Article  PubMed  Google Scholar 

  • Mondal, M, Chakrabarti A (2002) The tertiary amine local anesthetic dibucaine binds to the membrane skeletal protein spectrin. FEBS Lett 532:396–400

    Article  PubMed  CAS  Google Scholar 

  • Morgan GW, Allen CL, Jeffries TR, Hollinshead M, Field MC (2001) Developmental and morphological regulation of clathrin-mediated endocytosis in Trypanosoma brucei. J Cell Sci 114:2605–2615

    PubMed  CAS  Google Scholar 

  • Porto-Carreiro I, Attias M, Miranda K, De Souza W, Cunha-e-Silva N (2000) Trypanosoma cruzi epimastigotes endocytic pathway: cargo enters the cytostome and passes through an early endosomal network before storage in reservosomes. Eur J Cell Biol 79(11):858–869

    Article  PubMed  CAS  Google Scholar 

  • Sengupta S, Tripathi J, Tandon R, Raje M, Roy RP, Basu SK, Mukhopadhyay A (1999) Hemoglobin endocytosis in Leishmania is mediated through a 46-kDa protein located in the flagellar pocket. J Biol Chem 274:2758–2765

    Article  PubMed  CAS  Google Scholar 

  • Shapiro SZ, Webster P (1989) Coated vesicles from the protozoan parasite Trypanosoma brucei: purification and characterization. J Protozool 36:344–349

    PubMed  CAS  Google Scholar 

  • Soares MJ, De Souza W (1991) Endocytosis of gold-labeled proteins and LDL by Trypanosoma cruzi. Parasitol Res 77:461–468

    Article  PubMed  CAS  Google Scholar 

  • Soares MJ, Souto-Padrón T, De Souza W (1992) Identification of a large pre-lysosomal compartment in the pathogenic protozoon Trypanosoma cruzi. J Cell Sci 102:157–167

    PubMed  CAS  Google Scholar 

  • Souto-Padrón T, Campetella OE, Cazzulo JJ, De Souza W (1990) Cysteine proteinase in Trypanosoma cruzi: immunocytochemical localization and involvement in parasite–host cell interaction. J Cell Sci 96:485–490

    PubMed  Google Scholar 

  • Tolleshaugh H, Trond B, Holte K (1982) Effects of local anesthetics and relate compounds on the endocytosis and catabolism of asialo-glycoproteins in isolated hepatocytes. Biochim Biophys Acta 714:114–121

    PubMed  Google Scholar 

  • Webster P (1989) Endocytosis in African trypanosomes I. Three dimensional structure of the endocytic organelles in Trypanosoma brucei and T. congolense. Eur J Cell Biol 49:295–302

    PubMed  CAS  Google Scholar 

  • Webster P, Fish WR (1989) Endocytosis in African trypanosomes II. Occurrence in different life-cycle stages and intracellular sorting. Eur J Cell Biol 49:3003–3010

    Google Scholar 

  • Weise F, Stierhof YD, Kuhn C, Weise M, Overath P (2000) Distribution of GPI-anchored proteins in the protozoan parasites Leishmania based on an improved ultrastructural description using high-pressure frozen cells. J Cell Sci 113:4587–4603

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Thaïs Souto-Padrón.

Additional information

This review was presented at the International Symposium on Vesicle Trafficking in Parasitic Protozoa.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Souto-Padrón, T., Lima, A.P. & de Oliveira Ribeiro, R. Effects of dibucaine on the endocytic/exocytic pathways in Trypanosoma cruzi . Parasitol Res 99, 317–320 (2006). https://doi.org/10.1007/s00436-006-0192-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00436-006-0192-1

Keywords

Navigation