FK506 promotes adenosine release from endothelial cells via inhibition of adenosine kinase

被引:21
作者
Hwang, KK [1 ]
Hall, CS [1 ]
Spielman, WS [1 ]
Sparks, HV [1 ]
机构
[1] Michigan State Univ, Dept Physiol, E Lansing, MI 48824 USA
关键词
FK506; adenosine; adenosine kinase; endothelial cell;
D O I
10.1016/S0014-2999(01)01179-7
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The immunosuppressants, cyclosporin A and tacrolimus (FK506) induce an increase in plasma levels of adenosine and mimic ischemic preconditioning. However. the mechanism of action of the two drugs on adenosine metabolism is not clear. Since inhibition of adenosine kinase promotes an increase in endogenous adenosine release. we tested a hypothesis that FK506 induces adenosine release via inhibition of adenosine kinase activity. In cultured endothelial cells. FK506 enhanced release of tracer adenosine and inhibited uptake of tracer adenosine. It also reduced adenosine kinase activity of the cell membrane fraction. In addition, FK506 does not inhibit membrane transport of tracer adenosine. These observations indicate that FK506 inhibits in situ adenosine kinase activity in endothelial cells. Other cell signaling inhibitors were found to inhibit adenosine uptake via inhibition of adenosine transport. In conclusion., FK506 promotes adenosine release from endothelial cells by a novel mechanism involving inhibition of adenosine kinase activity associated with the membrane. (C) 2001 Published by Elsevier Science B.V.
引用
收藏
页码:85 / 93
页数:9
相关论文
共 42 条
[1]  
ANDRES CM, 1979, J BIOL CHEM, V254, P1388
[2]   THE ACUTE EFFECT OF FK506 AND CYCLOSPORINE ON ENDOTHELIAL-CELL FUNCTION AND RENAL VASCULAR-RESISTANCE [J].
BENIGNI, A ;
MORIGI, M ;
PERICO, N ;
ZOJA, C ;
AMUCHASTEGUI, CS ;
PICCINELLI, A ;
DONADELLI, R ;
REMUZZI, G .
TRANSPLANTATION, 1992, 54 (05) :775-780
[3]   2 DISTINCT SIGNAL TRANSMISSION PATHWAYS IN LYMPHOCYTES-T ARE INHIBITED BY COMPLEXES FORMED BETWEEN AN IMMUNOPHILIN AND EITHER FK506 OR RAPAMYCIN [J].
BIERER, BE ;
MATTILA, PS ;
STANDAERT, RF ;
HERZENBERG, LA ;
BURAKOFF, SJ ;
CRABTREE, G ;
SCHREIBER, SL .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1990, 87 (23) :9231-9235
[4]  
Bochelen D, 1999, J PHARMACOL EXP THER, V288, P653
[5]   ADENINE-NUCLEOTIDE RELEASE FROM ISOLATED PERFUSED GUINEA-PIG HEARTS AND EXTRACELLULAR FORMATION OF ADENOSINE [J].
BORST, MM ;
SCHRADER, J .
CIRCULATION RESEARCH, 1991, 68 (03) :797-806
[6]   The anti-inflammatory potential of adenosine in ischemia-reperfusion injury: Established and putative beneficial actions of a retaliatory metabolite [J].
Bouma, MG ;
vandenWildenberg, FAJM ;
Buurman, WA .
SHOCK, 1997, 8 (05) :313-320
[7]  
Bouma MG, 1997, J IMMUNOL, V158, P5400
[8]   Sites of action for future therapy:: an adenosine-dependent mechanism by which aspirin retains its antiinflammatory activity in cyclooxygenase-2 and NFκB knockout mice [J].
Cronstein, BN ;
Montesinos, MC ;
Weissmann, G .
OSTEOARTHRITIS AND CARTILAGE, 1999, 7 (04) :361-363
[9]   THE ANTIINFLAMMATORY EFFECTS OF AN ADENOSINE KINASE INHIBITOR ARE MEDIATED BY ADENOSINE [J].
CRONSTEIN, BN ;
NAIME, D ;
FIRESTEIN, G .
ARTHRITIS AND RHEUMATISM, 1995, 38 (08) :1040-1045
[10]   Salicylates and sulfasalazine, but not glucocorticoids, inhibit leukocyte accumulation by an adenosine-dependent mechanism that is independent of inhibition of prostaglandin synthesis and p105 of NFκB [J].
Cronstein, BN ;
Montesinos, MC ;
Weissmann, G .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (11) :6377-6381