ArticleThe Journal of physiology2000
Effects of the immunosuppressant FK506 on intracellular Ca2+ release and Ca2+ accumulation mechanisms.
Article in The Journal of physiology, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 73 citations in OpenAlex.
- An Immune-Independent Mode of Action of Tacrolimus in Promoting Human Extravillous Trophoblast Migration Involves Intracellular Calcium Release and F-Actin Cytoskeletal Reorganization.International journal of molecular sciences · 2024Article
- The calcineurin regulator Sarah enables distinct forms of homeostatic plasticity at theFrontiers in synaptic neuroscience · 2022Article
- Article
- FK506 regulates CaBritish journal of pharmacology · 2020Article
- Effects of inhibiting mTOR with rapamycin on behavior, development, neuromuscular physiology and cardiac function in larvalBiology open · 2019Article
- Recent Topics on The Mechanisms of Immunosuppressive Therapy-Related Neurotoxicities.International journal of molecular sciences · 2019Review
- Review
- Unraveling the role of peptidyl-prolyl isomerases in neurodegeneration.Molecular neurobiology · 2011Review
- Regulation by FK506 and rapamycin of Ca2+ release from the sarcoplasmic reticulum in vascular smooth muscle: the role of FK506 binding proteins and mTOR.British journal of pharmacology · 2009Article
- Regulation of inositol 1,4,5-trisphosphate-induced Ca2+ release by reversible phosphorylation and dephosphorylation.Biochimica et biophysica acta · 2009Review
- GPI-1046 protects dorsal root ganglia from gp120-induced axonal injury by modulating store-operated calcium entry.Journal of the peripheral nervous system : JPNS · 2009Article
- Role of initial protein phosphorylation events and localized release-activated calcium influx in B cell antigen receptor signaling.Journal of leukocyte biology · 2009Article
- Removal of FKBP12.6 does not alter the conductance and activation of the cardiac ryanodine receptor or the susceptibility to stress-induced ventricular arrhythmias.The Journal of biological chemistry · 2007Article
- Ca2+-sparks constitute elementary building blocks for global Ca2+-signals in myocytes of retinal arterioles.Cell calcium · 2007Article
- Inositol trisphosphate receptor Ca2+ release channels.Physiological reviews · 2007Review
- Expression profiling of laser-microdissected intrapulmonary arteries in hypoxia-induced pulmonary hypertension.Respiratory research · 2005Article
- The inhibition of the sarcoplasmic/endoplasmic reticulum Ca2+-ATPase by macrocyclic lactones and cyclosporin A.The Biochemical journal · 2002Article
- Modulation of type-1 Ins(1,4,5)P3 receptor channels by the FK506-binding protein, FKBP12.The Biochemical journal · 2002Article
- Human Trp3 forms both inositol trisphosphate receptor-dependent and receptor-independent store-operated cation channels in DT40 avian B lymphocytes.Proceedings of the National Academy of Sciences of the United States of America · 2001Article
- Characterization and mapping of the 12 kDa FK506-binding protein (FKBP12)-binding site on different isoforms of the ryanodine receptor and of the inositol 1,4,5-trisphosphate receptor.The Biochemical journal · 2001Article
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The immunophilin FKBP12 associates with intracellular Ca2+ channels and this interaction can be disrupted by the immunosuppressant FK506. We have investigated the effect of FK506 on Ca2+ release and Ca2+ uptake in permeabilized cell types. Changes in medium free [Ca2+] were detected by the fluorescent Ca2+ indicator fluo-3 in digitonin-permeabilized SH-SY5Y human neuroblastoma cells, DT40 and R23-11 (i.e. triple inositol 1,4,5-trisphosphate (IP3) receptor knockout cells) chicken B lymphocytes and differentiated and undifferentiated BC3H1 skeletal muscle cells. 45Ca2+ fluxes were studied in saponin-permeabilized A7r5 rat smooth muscle cells. Addition of FK506 to permeabilized SH-SY5Y cells led to a sustained elevation of the medium [Ca2+] corresponding to approximately 30 % of the Ca2+ ionophore A23187-induced [Ca2+] rise. This rise in [Ca2+] was not dependent on mitochondrial activity. This FK506-induced [Ca2+] rise was related to the inhibition of the sarcoplasmic/endoplasmic reticulum Ca2+-Mg2+-ATPase (SERCA) Ca2+ pump. Oxalate-facilitated 45Ca2+ uptake in SH-SY5Y microsomes was inhibited by FK506 with an IC50 of 19 microM. The inhibition of the SERCA Ca2+ pump was not specific since several macrocyclic lactone compounds (ivermectin > FK506, ascomycin and rapamycin) were able to inhibit Ca2+ uptake activity. FK506 (10 microM) did not affect IP3-induced Ca2+ release in permeabilized SH-SY5Y and A7r5 cells, but enhanced caffeine-induced Ca2+ release via the ryanodine receptor (RyR) in differentiated BC3H1 cells. In conclusion, FK506 inhibited active Ca2+ uptake by the SERCA Ca2+ pump; in addition, FK506 enhanced intracellular Ca2+ release through the RyR, but it had no direct effect on IP3-induced Ca2+ release.
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