Cyclosporin and tacrolimus increase plasma levels of adenosine in kidney transplanted patients.
The immunosuppressive agents, cyclosporin (CsA) and tacrolimus (FK506), display cardioprotective activities. The mechanism would consist on the inhibition of the enzyme, adenosine kinase (AK), leading to an increase in adenosine (ADO) levels. ADO, inosine (INO) and nucleotide plasma levels were measured in kidney transplant recipients before and 1, 2, 4, 6 and 8 h after the administration of CsA or FK506. After CsA and FK506 administration, ADO plasma levels significantly increased, reaching a peak level after 2 h (483 +/- 124 and 429 +/- 96 nm, respectively), and then progressively declined. Calculated peak values (t(max)) of ADO were slightly delayed with respect to those of CsA and FK506. Treatment with rapamycin did not influence the phenomenon. The dynamic profile of plasma changes of ADO, nucleotides and INO were consistent with the inhibition of the enzyme, AK. ADO increase may be clinically relevant in terms of anti-ischaemic, tissue protecting, and immunosuppressive activities as well as in terms of nephrotoxicity.
Capecchi
Pier Leopoldo
PL
Department of Clinical Medicine and Immunological Science, Section of Clinical Immunology, University of Siena, Policlinico Le Scotte, 53100 Siena, Italy. capecchipl@unisi.it
Rechichi
Serena
S
Lazzerini
Pietro Enea
PE
Collini
Andrea
A
Guideri
Francesca
F
Ruggieri
Giuliana
G
Carmellini
Mario
M
Laghi-Pasini
Franco
F
D000241:Adenosine / Q000097:blood*; D000328:Adult; D000368:Aged; D016572:Cyclosporine / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D016559:Tacrolimus / Q000494:pharmacology*
D007166:Immunosuppressive Agents; D016572:Cyclosporine; D000241:Adenosine; D016559:Tacrolimus