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Related Experiment Videos

Cyclosporin A and FK506 decrease adenosine kinase activity and adenosine uptake in T-lymphocytes.

Jozef Spychala1, Beverly S Mitchell

  • 1Departments of Pharmacology and Internal Medicine, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599, USA. jozek@med.unc.edu

The Journal of Laboratory and Clinical Medicine
|September 14, 2002
PubMed
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Cyclosporin A and FK506 increase extracellular adenosine levels in T-lymphocytes by inhibiting adenosine kinase (AK) activity. This mechanism enhances adenosine concentrations, impacting immune function.

Area of Science:

  • Immunology
  • Biochemistry
  • Pharmacology

Background:

  • Adenosine is a key immune modulator.
  • Adenosine kinase (AK) regulates adenosine metabolism.
  • AK activity is crucial for adenosine regulation in T-lymphocytes.

Purpose of the Study:

  • To investigate the effect of immunosuppressive drugs on adenosine uptake and AK activity in T-lymphocytes.
  • To elucidate the mechanism by which cyclosporin A (CsA) and FK506 influence adenosine levels.

Main Methods:

  • Measuring adenosine uptake and AK activity in activated T-lymphocytes.
  • Assessing the impact of CsA and FK506 on adenosine uptake and AK activity.
  • Evaluating the selectivity of drug inhibition for adenosine uptake.

Related Experiment Videos

Main Results:

  • Adenosine uptake and AK activity significantly increased during T-lymphocyte activation.
  • CsA and FK506 inhibited both adenosine uptake and AK activity in a dose-dependent manner.
  • Drug treatment led to increased extracellular adenosine levels, suggesting AK inhibition is the primary mechanism.

Conclusions:

  • CsA and FK506 enhance extracellular adenosine concentrations in T-lymphocytes.
  • This effect is mediated by the inhibition of adenosine kinase (AK) activity.
  • The findings highlight a novel mechanism of immunosuppression involving adenosine regulation.