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Clinical Chemistry 43: 2312-2317, 1997;
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(Clinical Chemistry. 1997;43:2312-2317.)
© 1997 American Association for Clinical Chemistry, Inc.

Articles

IMP-dehydrogenase inhibition in human lymphocytes and lymphoblasts by mycophenolic acid and mycophenolic acid glucuronide

Andrea Griesmacher1,2,a, Günter Weigel2, Gernot Seebacher2 and Mathias M. Müller1

1 Ludwig-Boltzmann-Institute for Cardiothoracic Surgical Research at the Institute of Laboratory Diagnostics, Kaiser-Franz-Josef-Hospital, Kundratstr. 3, A-1100 Vienna, Austria.

2 Department of Cardiothoracic Surgery, Clinical Biochemistry, University of Vienna, Währinger Gürtel 18–20, A-1090 Vienna, Austria.
a Author for correspondence. Fax +43-1-60191-3309.

Inosine 5'-monophosphate dehydrogenase (IMP-DH) activities were measured in human lymphocytes (exhibiting type I IMP-DH activity) and human lymphoblasts (exhibiting type II IMP-DH activity) in the presence of various amounts of mycophenolic acid (MPA) (0–20 µmol/L) and MPA glucuronide (MPAG) (0–200 µmol/L). Moreover, the influences of human serum albumin (HSA) and human plasma on the MPA- and MPAG-mediated effects were investigated. In the presence of water, 2.5 µmol/L MPA decreased the IMP-DH activity measured in lymphocytes by 60%, whereas in lymphoblasts a 80% inhibition was detectable. In the presence of >=10 µmol/L MPA, lymphocytic as well as lymphoblastic IMP-DH activities were reduced in a similar manner. The concentration of MPAG required for 50% inhibition was for both cell types >25 µmol/L and <50 µmol/L, respectively. MPAG (200 µmol/L) reduced lymphocytic as well as lymphoblastic IMP-DH activity by ~80%. With 100 g/L HSA or human plasma as diluent, the inhibitory effects of MPA and MPAG were significantly (P <0.05) diminished, whereas HSA concentrations <=25 g/L only slightly influenced the inhibition of IMP-DH activity by MPA and MPAG. In summary, it can be clearly demonstrated that not only MPA but also MPAG contributes to the inhibition of both IMP-DH isoenzymes, which might be relevant for the immunosuppressive properties of mycophenolate mofetil in transplant patients.




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