How does fk506 work

Furthermore, in resting adult rat cardiac myocytes treated with the immunosuppressant, McCall et al.

Although the positive inotropic action of FK is thought to arise from its ability to alter the open probability of the ryanodine receptor 4 , duBell et al. Rats and rabbits also show age-dependent increases in ryanodine receptor function and SR contributions to excitation-contraction coupling 20 — These changes are consistent with extensive calcification of cardiac tissue described in a tacrolimus-treated transplant recipient 23 and may be linked to the appearance of cardiomyopathies in children treated with this immunosuppressant.

J Biol Chem : — Marks AR Intracellular calcium-release channels: regulators of cell life and death. Am J Physiol : H—H J Physiol : — Lancet 1 : — Article Google Scholar.

Am J Cardiol 81 : — Transplantation 66 : — Transplant Proc 26 : — Pediatr Res 40 : 59— Google Scholar. Hove-Madsen L, Bers DM Indo-1 binding to protein in permeabilized ventricular myocytes alters its spectral and Ca binding properties. Biophys J 63 : 89— Li Q, Altschuld RA, Stokes BT Quantitation of intracellular free calcium in single adult cardiomyocytes by fura-2 fluorescence microscopy: calibration of fura-2 ratios.

Biochem Biophys Res Commun : — Haworth RA Quantitation of intracellular free calcium in single myocytes by Fura-2 fluorescence microscopy. Cell Calcium 10 : — Circ Res 79 : — J Physiol : 3: — J Mol Cell Cardiol 18 : — Pediatr Res 31 : — Wibo M, Bravo G, Godfraind T Postnatal maturation of excitation-contraction coupling in rat ventricle in relation to the subcellular localization and surface density of 1,4-dihydropyridine and ryanodine receptors.

Circ Res 68 : — Transplantation 64 : — Download references. The authors thank James Hensley for technical assistance. FK was kindly provided by Fujisawa Pharmaceutical Co. Related Products Related Products. Educational Materials 3 Wallchart. Mini Review. Product Applications This product is designed for use in the following research area s as part of the highlighted workflow stage s.

Research Area. Item added to your cart FK One of our representatives will be happy to help you by telephone or email. Please complete the form to contact us by email. A representative will get back to you shortly. Outlying Islands U. Please select a region, state or province. All rights reserved. Document Type Product Information Sheet. Here we discuss recent findings, including our own, which highlight differences in efficacy and mechanisms between CsA and FK As a result, several signal transduction pathways become operational, leading to induction of cytokine gene expression and stimulation of cellular activation Figure 1.

Site of action of cyclosporin A and FK It had therefore been anticipated that the immunosuppressive effects of CsA and FK are almost identical, and mediated via antagonism of calcineurin activity. Recent experimental results [ 10 ; Almawi et al.

This is a very important difference between FK and CsA, the latter of which is ineffective in the treatment of allograft rejection [ 11 ]. While the exact cellular and molecular targets of FK remain to be investigated, the use of FK in combating refractory allograft rejection episodes [ 11 , 12 , 19 ] appears rational in view of the above findings.

Correspondence and offprint requests to : Dr Wassim Y. Identification of calcineurin as a key signalling enzyme in T lymphocyte activation. Nature ; : — Kunz J, Hall MN. Cyclosporin A, FK, and rapamycin: more than just immunosuppression. Trends Biochem Sci ; 18 : — Clin Transplant ; 13 : — Eur J Pharmacol ; : 51 — Halloran PF. Molecular mechanisms of new immunosuppressants. Clin Transplant ; 10 : — Distinct tissue and cellular distribution of two major isoforms of calcineurin.

Mol Immunol ; 34 : — The mechanism of action of cyclosporin A and FK Clin Immunol Immunopathol ; 80 : S40 — Two distinct signal transmission pathways in T lymphocytes are inhibited by complexes formed between an immunophilin and either FK or rapamycin.

J Pharmacol Exp Ther ; 55 : — Cyclosporin A and tacrolimus FK suppress expression of inducible nitric oxide synthase in vitro by different mechanisms. Br J Pharmacol ; : — Jiang H, Kobayashi M.

Differences between cyclosporin A and tacrolimus in organ transplantation. Transplant Proc ; 31 : — Efficacy of tacrolimus in the treatment of refractory rejection in heart and lung transplant recipients. J Heart Lung Transplant ; 18 : — The effect of cyclosporin A, FK, and rapamycin on the murine contact sensitivity reaction. Clin Exp Immunol ; : — J Immunol ; : — Differences in type 1 and type 2 intracytoplasmic cytokines, detected by flow cytometry, according to immunosuppression cyclosporin A vs.