Receptor-mediated cellular uptake of cyclosporine.
نویسندگان
چکیده
THE PROCESS of cellular uptake and metabolism of cyclosporine (CsA) is poorly understood. Earlier studies in this laboratory indicated that transport of CsA in blood occurs in association with plasma lipoproteins, with low density lipoprotein (LDL) and high density lipoprotein (HOL) carrying about 32% each of the total CsA in blood. This observation suggests the possibility that the cellular uptake of CsA may occur through the LDL receptor pathway. To further identify this phenomenon, we incubated CsA-LOL complex with freshly isolated peripheral blood lymphocytes (PBL) and also with PBL in which LDL receptors synthesis was enhanced by incubation in lipid free serum. Results of these experiments show that cellular uptake of CsA is increased about 25% in cells incubated in lipid-free serum relative to controls. This increased uptake of CsA could be in part due to the proliferation of LDL receptors in the stimulated cells. Since at least 32% of the drug circulates in association with LDL, this pathway provides an important mechanism for the meta bolism of CsA. The aims of this study were to examine the kinetics of binding and uptake of CsA by the human peripheral blood lymphocytes. and the enhancement of CsA uptake by peripheral blood lymphocytes via LOL receptor pathway. Cyclosporine (CsA) is widely used in transplantation as the immunosuppressive agent of choice. In our earlier studies. we have shown that transport of CsA in blood occurs mainly in association with plasma lipoproteins. 70% of the drug being in LDL and HOL fractions.! This suggests that cellular uptake and metabolism of CsA may. at least in part. follow the lipoprotein metabolism. specifically. the LOLreceptor mediated pathway.
منابع مشابه
Nanolipoparticles-mediated MDR1 siRNA delivery: preparation, characterization and cellular uptake
Objective(s): Lipid-based nanoparticles (NLP) are PEGylated carriers composed of lipids and encapsulated nucleic acids with a diameter less than 100 nm. The presence of PEG in the NLP formulation improves the particle pharmacokinetic behavior. The purpose of this study was to prepare and characterize NLPs containing MDR1 siRNA and evaluate their cytotoxicity and cellular uptake. MDR1 siRNA coul...
متن کاملEffect of uptake transporters OAT3 and OATP1B1 and efflux transporter MRP2 on the pharmacokinetics of eluxadoline
The effects of OATP1B1, OAT3, and MRP2 on the pharmacokinetics of eluxadoline, an oral, locally active, opioid receptor agonist/antagonist being developed for treatment of IBS-d were assessed in vivo. Coadministration of a single 200 mg dose of eluxadoline with cyclosporine, and probenecid increased eluxadoline systemic exposure [AUC(0-inf) ] by 4.4- and 1.4-fold, respectively, whereas peak exp...
متن کاملFK-506 enhances cyclosporine uptake by peripheral blood lymphocytes.
T HE PROCESS of cellular uptake and metabolism of cyclosporine (CsA) is poorly understood. Previously, we have shown that the transport of CsA in blood occurs in association with plasma Iipoproteins,l with low-density lipoprotein (LOL), and with highdensity lipoprotein, each transporting about 32% of the total amount of CsA in blood. This observation raises the possibility that further cellular...
متن کاملThe effect of ketamine on NMDA receptor-mediated LTP depends on ketamine effects on non-NMDA-mediated synaptic transmission in CA1 area of rat hippocampal slices
It has been reported that ketamine as an uncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist has also non-NMDA receptor antagonist properties. We recently found that ketamine (20 ?M) affected differently induction of NMDA receptor-mediated long-term potentiation (LTP) when administered 30 min prior to tetanic Primed-Bursts (PBs) stimulation. On the other hand, ketamine also influenced...
متن کاملThe Cytotoxicity of Silver Nanoparticles Coated with Different Proteins on Balb/c Macrophage Cells
Background and Aims: Coated nanoparticles have different surface chemistry, aggregation, and interaction properties. The aim of this study was to investigate the cytotoxicity of silver nanoparticles AgNPs coated with different proteins on Balb/c macrophages. Materials and Methods: In this study these items were evaluated: 1) the size of aggregation, 2) the quantity and mechanisms of uptake, ...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Transplantation proceedings
دوره 21 1 Pt 1 شماره
صفحات -
تاریخ انتشار 1989