Trypanosoma cruzi: Alteration of cAMP metabolism following infection of human endothelial cells

Stephen A. Morris, Herbert Tanowitz, Maynard Makman, Victor B. Hatcher, John P. Bilezikian, Murray Wittner

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

We have previously reported that Trypanosoma cruzi infection of endothelial cells results in alterations in the metabolism of Ca2+, inositol triphosphate(IP3), and prostacycline (PGI2). In this report, we demonstrate that infection also alters the metabolism of cAMP. Infection of endothelial cells does not significantly alter β-adrenergic receptor density or affinity, adenylate cyclase activity, and whole-cell cAMP levels. However, incubation of infected endothelial cells with the phosphodiesterase inhibitor isobutylmethylxanthine (IBMX) resulted in less than a 60% increase in cell cAMP in contrast to the greater than a 100% increase observed in uninfected endothelial cells under otherwise identical reaction conditions. Infected endothelial cells demonstrated a twofold increase in phosphodiesterase activity when measured directly. Moreover, homogenates prepared from infected endothelial cells previously incubated with isoproterenol for 20 min showed little or no change in PDE activity. In contrast, homogenates prepared from uninfected endothelial cells treated under otherwise identical reaction conditions showed a 5.7-fold increase in PDE activity. In the presence of IBMX, isoproterenol-dependent stimulation of cAMP levels in infected endothelial cells reached a maximum level at 5 min of incubation, and thereafter rapidly declined. In contrast, cAMP levels in uninfected endothelial cells reached a maximum at 2 min of incubation, and thereafter remained elevated throughout the duration of the incubation. Infection-associated changes in isoproterenol dependent stimulation of cAMP accumulation appear to relate, in part, to changes in PDE activity.

Original languageEnglish (US)
Pages (from-to)69-76
Number of pages8
JournalExperimental Parasitology
Volume74
Issue number1
DOIs
StatePublished - Feb 1992

Keywords

  • Endothelial cells
  • Hemoflagellates
  • Trypanosoma cruzi

ASJC Scopus subject areas

  • Parasitology
  • Immunology
  • Infectious Diseases

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