Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0024312 (
lymphopenia
)
4,859
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
SYL
-927 is a selective sphingosine-1-phosphate receptor 1 (S1P
1
) agonist for autoimmune diseases. It undergoes phosphorylation to the active
SYL
-927-P
in vivo
, which activates S1P
1
on lymphocytes, causing
lymphopenia
by retention of lymphocytes in the lymph nodes. The aim of this study was to identify the involvement of blood cells in the phosphorylation of
SYL
-927. In addition, pharmacokinetics of
SYL
-927 and
SYL
-927-P in blood and plasma were compared in rats. The results demonstrated that
SYL
-927 can be converted to
SYL
-927-P in rat blood, but not in rat plasma. However, both rat blood and plasma are capable of dephosphorylating
SYL
-927-P to
SYL
-927.
SYL
-927-P generation and release were observed after incubating
SYL
-927 with rat and human erythrocytes and platelets. The addition of sphingosine kinases (SPHKs) inhibitors
N
,
N
-dimethylsphingosine (DMS) and FTY720 significantly inhibited
SYL
-927-P generation, indicating the involvement of SPHKs. In addition,
SYL
-927 and
SYL
-927-P levels in blood were significantly higher than those in plasma after oral administration of
SYL
-927 in rats, suggesting the blood cells for the production of
SYL
-927-P. In summary, the blood cells such as erythrocytes and platelets contribute to the generation and release of
SYL
-927-P, which is important for maintaining plasma active phosphate levels for prolonged effects.
...
PMID:The involvement of blood cells in the phosphorylation of the selective sphingosine-1-phosphate receptor 1 agonist SYL-927. 3078 60
