Abstract
6-MP inhibitory effects on the MLR were reversed by AIC (46%), adenine (32%), hypoxanthine (89%), adenosine (86%) and inosine (93%). AIC, adenine, hypoxanthine and inosine had no effect on azathioprine inhibition of the MLR. Adenosine at 10 microM caused 29% reversal and had no effect at 100-400 microM on azathioprine inhibition of the MLR. Reversal of 6-MP suppression of the MLR was decreased with the delay of adenosine addition. Guanine, xanthine and guanosine caused no reversal of 6-MP or azathioprine inhibitory effects on the MLR. These results show that azathioprine and 6-MP suppress the MLR by different mechanisms.
Full text
PDF
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Al-Safi S. A., Maddocks J. L. Effects of azathioprine on the human mixed lymphocyte reaction (MLR). Br J Clin Pharmacol. 1983 Feb;15(2):203–209. doi: 10.1111/j.1365-2125.1983.tb01487.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Allison A. C., Hovi T., Watts R. W., Webster A. D. The role of de novo purine synthesis in lymphocyte transformation. Ciba Found Symp. 1977;(48):207–224. doi: 10.1002/9780470720301.ch13. [DOI] [PubMed] [Google Scholar]
- Bach F. H., Voynow N. K. One-way stimulation in mixed leukocyte cultures. Science. 1966 Jul 29;153(3735):545–547. doi: 10.1126/science.153.3735.545. [DOI] [PubMed] [Google Scholar]
- Bach J. F., Dardenne M., Fournier C. In vitro evaluation of immunosuppressive drugs. Nature. 1969 Jun 7;222(5197):998–999. doi: 10.1038/222998a0. [DOI] [PubMed] [Google Scholar]
- Bøyum A. Isolation of lymphocytes, granulocytes and macrophages. Scand J Immunol. 1976 Jun;Suppl 5:9–15. [PubMed] [Google Scholar]
- Castles J. J., Gershwin M. E., Saito W., Ardans A., Osburn B. The activity of purine salvage pathway enzymes in murine and horse models of congenital and acquired dysimmunity. Dev Comp Immunol. 1977 Apr;1(2):165–173. doi: 10.1016/s0145-305x(77)80009-8. [DOI] [PubMed] [Google Scholar]
- Chalmers A. H. Studies on the mechanism of formation of 5-mercapto-1-methyl-4-nitroimidazole, a metabolite of the immunosuppressive drug azathioprine. Biochem Pharmacol. 1974 Jul 1;23(13):1891–1901. doi: 10.1016/0006-2952(74)90198-1. [DOI] [PubMed] [Google Scholar]
- ELION G. B., SINGER S., HITCHINGS G. H. The purine metabolism of a 6-mercaptopurine-resistant Lactobacillus casei. J Biol Chem. 1953 Sep;204(1):35–41. [PubMed] [Google Scholar]
- Elion G. B. Symposium on immunosuppressive drugs. Biochemistry and pharmacology of purine analogues. Fed Proc. 1967 May-Jun;26(3):898–904. [PubMed] [Google Scholar]
- HAKALA M. T., NICHOL C. A. PREVENTION OF THE GROWTH-INHIBITORY EFFECT OF 6-MERCAPTOPURINE BY 4-AMINOIMIDAZOLE-5-CARBOXAMIDE. Biochim Biophys Acta. 1964 Apr 27;80:665–668. doi: 10.1016/0926-6550(64)90311-1. [DOI] [PubMed] [Google Scholar]
- Henderson J. F., Brox L. W., Kelley W. N., Rosenbloom F. M., Seegmiller J. E. Kinetic studies of hypoxanthine-guanine phosphoribosyltransferase. J Biol Chem. 1968 May 25;243(10):2514–2522. [PubMed] [Google Scholar]
- Hitchings G. H. Symposium on immunosuppressive drugs. Summary and concluding remarks. Fed Proc. 1967 May-Jun;26(3):958–960. [PubMed] [Google Scholar]
- McGuire T. C., Pollara B., Moore J. J., Poppie M. J. Evaluation of adenosine deaminase and other purine salvage pathway enzymes in horses with combined immunodeficiency. Infect Immun. 1976 Mar;13(3):995–997. doi: 10.1128/iai.13.3.995-997.1976. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mehrishi J. N., Grassetti D. R. Sulphydryl groups on the surface of intact Ehrlich ascites tumour cells, human blood platelets and lymphocytes. Nature. 1969 Nov 8;224(5219):563–564. doi: 10.1038/224563a0. [DOI] [PubMed] [Google Scholar]
- TOMIZAWA S., ARONOW L. Studies on drug resistance in mammalian cells. II. 6-Mercaptopurine resistance in mouse fibroblasts. J Pharmacol Exp Ther. 1960 Feb;128:107–114. [PubMed] [Google Scholar]