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IMP-dehydrogenase inhibition in human lymphocytes and lymphoblasts by mycophenolic acid and mycophenolic acid glucuronide.
Clin Chem. 1997 Dec; 43(12):2312-7.CC

Abstract

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 mumol/L) and MPA glucuronide (MPAG) (0-200 mumol/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 mumol/L MPA decreased the IMP-DH activity measured in lymphocytes by 60%, whereas in lymphoblasts a 80% inhibition was detectable. In the presence of > or = 10 mumol/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 mumol/L and < 50 mumol/L, respectively. MPAG (200 mumol/L) reduced lymphocytic as well as lymphoblastic IMP-DH activity by approximately 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 < or = 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.

Authors+Show Affiliations

Ludwig-Boltzmann-Institute for Cardiothoracic Surgical Research, Kaiser-Franz-Josef-Hospital, Vienna, Austria.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

9439448

Citation

Griesmacher, A, et al. "IMP-dehydrogenase Inhibition in Human Lymphocytes and Lymphoblasts By Mycophenolic Acid and Mycophenolic Acid Glucuronide." Clinical Chemistry, vol. 43, no. 12, 1997, pp. 2312-7.
Griesmacher A, Weigel G, Seebacher G, et al. IMP-dehydrogenase inhibition in human lymphocytes and lymphoblasts by mycophenolic acid and mycophenolic acid glucuronide. Clin Chem. 1997;43(12):2312-7.
Griesmacher, A., Weigel, G., Seebacher, G., & Müller, M. M. (1997). IMP-dehydrogenase inhibition in human lymphocytes and lymphoblasts by mycophenolic acid and mycophenolic acid glucuronide. Clinical Chemistry, 43(12), 2312-7.
Griesmacher A, et al. IMP-dehydrogenase Inhibition in Human Lymphocytes and Lymphoblasts By Mycophenolic Acid and Mycophenolic Acid Glucuronide. Clin Chem. 1997;43(12):2312-7. PubMed PMID: 9439448.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - IMP-dehydrogenase inhibition in human lymphocytes and lymphoblasts by mycophenolic acid and mycophenolic acid glucuronide. AU - Griesmacher,A, AU - Weigel,G, AU - Seebacher,G, AU - Müller,M M, PY - 1998/1/24/pubmed PY - 1998/1/24/medline PY - 1998/1/24/entrez SP - 2312 EP - 7 JF - Clinical chemistry JO - Clin. Chem. VL - 43 IS - 12 N2 - 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 mumol/L) and MPA glucuronide (MPAG) (0-200 mumol/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 mumol/L MPA decreased the IMP-DH activity measured in lymphocytes by 60%, whereas in lymphoblasts a 80% inhibition was detectable. In the presence of > or = 10 mumol/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 mumol/L and < 50 mumol/L, respectively. MPAG (200 mumol/L) reduced lymphocytic as well as lymphoblastic IMP-DH activity by approximately 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 < or = 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. SN - 0009-9147 UR - https://www.unboundmedicine.com/medline/citation/9439448/IMP_dehydrogenase_inhibition_in_human_lymphocytes_and_lymphoblasts_by_mycophenolic_acid_and_mycophenolic_acid_glucuronide_ L2 - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&amp;PAGE=linkout&amp;SEARCH=9439448.ui DB - PRIME DP - Unbound Medicine ER -