Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0024312 (lymphopenia)
 4,859 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The major sphingolipid metabolite sphingosine-1-phosphate (S1P) plays a central role in maintaining the homeostasis of lymphocyte motility. S1P is the ligand for a family of five GPCRs termed S1P1 to S1P5, each with distinct signaling pathways. The significance of S1P in immune cell regulation was revealed when the immunomodulator fingolimod (Mitsubishi Tanabe Pharma Corp/Novartis AG) was discovered to cause lymphopenia via S1P1 signaling. Clinical trials have targeted S1P1 receptor modulators for autoimmune diseases, particularly for the potential treatment of multiple sclerosis (MS) and the prevention of transplant rejection. This review highlights the potential use of S1P receptor modulation in the clinic and summarizes the clinical experience with these compounds in MS and transplant rejection.
 ...
PMID:The role of sphingosine-1-phosphate receptor modulators in the prevention of transplant rejection and autoimmune diseases. 1987 86

Sphingosine-1-phosphate (S1P) is a major bioactive phospholipid, which binds to and activates a family of five G-protein-coupled receptors designated as S1P 1 (S1P1) through S1P5. The S1P1 receptor subtype, expressed primarily on lymphocytes, is known to play a critical role in the regulation of lymphocyte trafficking. S1P1 inhibitors result in the inhibition of lymphoid cell trafficking and are of interest to treat various inflammatory conditions. In this study, we describe a gastric finding associated with oral gavage administration of a small molecule S1P1 inhibitor to Sprague-Dawley rats. Rats were administered an S1P1 inhibitor once daily for 4 weeks and necropsies were conducted at the end of the dosing phase, and clinical pathology and histopathologic examination were performed. Lymphopenia and changes in lymphoid tissues were noted and were consistent with the pharmacodynamic effects for S1P1 inhibitory action. Histopathologic examination of the stomach revealed atrophy and depletion of gastric parietal cells in the glandular portion of the stomach. There are no literature data to suggest that this gastric effect is related to S1P1 pharmacology. Therefore, the mechanism of the observed gastric lesion is likely chemotype mediated.
...
PMID:Gastric parietal cell atrophy and depletion after administration of a sphingosine-1-phosphate 1 inhibitor. 2417 72