PMID: 8588225Dec 1, 1995Paper

Mode of action of tacrolimus (FK506): molecular and cellular mechanisms

Therapeutic Drug Monitoring
A W ThomsonA Zeevi

Abstract

Tacrolimus, formerly known as FK506, is a macrolide antibiotic with immunosuppressive properties. Although structurally unrelated to cyclosporin A (CsA), its mode of action is similar. It exerts its effects principally through impairment of gene expression in target cells. Tacrolimus bonds to an immunophilin, FK506 binding protein (FKBP). This complex inhibits calcineurin phosphatase. The drug inhibits calcium-dependent events, such as interleukin-2 gene transcription, nitric oxide synthase activation, cell degranulation, and apoptosis. Tacrolimus also potentiates the actions of glucocorticoids and progesterone by binding to FKBPs contained within the hormone receptor complex, preventing degradation. The agent may enhance expression of the transforming growth factor beta-1 gene in a fashion analogous to that demonstrated for CsA. T cell proliferation in response to ligation of the T cell receptor is inhibited by tacrolimus. Type 1 T helper cells appear to be preferentially suppressed compared with type 2 T helper cells. T cell-mediated cytotoxicity is impaired. B cell growth and antibody production are affected indirectly by the suppression of T cell-derived growth factors necessary for these functions. Antigen presentation app...Continue Reading

Citations

Dec 25, 2004·Catheterization and Cardiovascular Interventions : Official Journal of the Society for Cardiac Angiography & Interventions·Marc KollumChristoph Hehrlein
Sep 4, 2007·Rheumatology International·Yuji NozakiMasanori Funauchi
Nov 9, 2011·International Journal of Colorectal Disease·D RaptisCh Lazarides
Apr 1, 2009·Pflügers Archiv : European journal of physiology·S KettlewellG L Smith
Oct 14, 2005·Journal of Biomolecular NMR·Nadezhda V KovalevskayaJames Feeney
Dec 18, 2003·Clinics in Dermatology·Adrian M Goldstein
Oct 31, 2000·Journal of the Neurological Sciences·B C WhiteG S Krause
Oct 17, 2002·Respiratory Physiology & Neurobiology·Masayuki HanaokaKeishi Kubo
Sep 2, 1998·Transplantation Proceedings·A Cheung, A H Menkis
Dec 18, 2001·Brain Research. Developmental Brain Research·M AvramutC L Achim
Nov 30, 2000·International Journal of Dermatology·E J ZabawskiC J Cockerell
Sep 30, 2000·Kidney International·L V IvanovaD Proppe
Jan 29, 2002·Surgery·Domenica AltavillaFrancesco Squadrito
Aug 8, 2013·Pharmacogenetics and Genomics·Julia M BarbarinoRuss B Altman
Feb 6, 2004·Dermatologic Surgery : Official Publication for American Society for Dermatologic Surgery [et Al.]·Adam Z KawalekRobert G Phelps
Sep 8, 2000·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·G VoggenreiterF U Schade
Aug 23, 2002·Clinical Pharmacokinetics·Uwe ChristiansAlfonso Lampen
Jul 13, 2004·Clinical Pharmacokinetics·Christine E Staatz, Susan E Tett
Feb 23, 2013·World Journal of Gastroenterology : WJG·Jian-Jun YangHong-Wei Zhang
Feb 13, 2014·Clinica Chimica Acta; International Journal of Clinical Chemistry·Edward Ki Yun LeungKiang-Teck J Yeo
Jun 7, 2014·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Qi LiYuehong Xu
May 26, 2012·TheScientificWorldJournal·Guiling LiYan Liu
May 23, 2014·Journal of Controlled Release : Official Journal of the Controlled Release Society·Yingying HuangVenkatraman Subbu
Jan 15, 2016·Pulmonary Pharmacology & Therapeutics·Leah J WittMary E Strek
Jul 23, 2005·Journal of Investigative Surgery : the Official Journal of the Academy of Surgical Research·Michael SchäfferRichard Viebahn
Dec 8, 2011·Annals of Dermatology·In Su AhnCheol Heon Lee
Oct 28, 2014·The FEBS Journal·Swagatika SahooInes Thiele
Jul 19, 2013·Journal of Neuropathology and Experimental Neurology·Daniel SkukJacques P Tremblay
Jan 4, 2012·Pharmacology & Therapeutics·Michail I PapafaklisLampros K Michalis

❮ Previous
Next ❯

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis