Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.3.1.21 (CPT)
 4,580 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Using purified human T lymphocytes stimulated in serum-free media with adhered anti-CD3 + exogenous IL-2, we have shown that elevated [cAMP]i (mimicked by CPT-cAMP or induced by the physiological agonist PGE2) directly inhibits mitogen-induced 1) [3H]thymidine incorporation by PBMC, purified T cells, and isolated CD4+ and CD8+ T cell subpopulations; 2) expression of both high- and low-affinity IL-2 receptors; 3) plasma membrane expression of both p55 and p75 subunits of the IL-2 receptor; and 4) expression of p55 mRNA, but not p75 mRNA. The decrease in p55 mRNA is not due to enhanced mRNA metabolism. We conclude that elevated [cAMP]i, acting directly on T cells, inhibits mitogenesis by decreasing IL-2 receptor expression. We discuss the possible physiological relevance for the multiple stages of T cell activation that are sensitive to elevated [cAMP]i.
 ...
PMID:Cyclic AMP directly inhibits IL-2 receptor expression in human T cells: expression of both p55 and p75 subunits is affected. 184 80

The nerve growth factor (NGF) pathway has been shown to play a key role in pain treatment. Recently, a systems pharmacology model has been proposed that can aid in the identification and validation of drug targets in the NGF pathway. However, this model did not include the role of the p75 receptor, which modulates the signaling of NGF through the tropomyosin receptor kinase A (TrkA). The precise mechanism of the interaction between these two receptors has not been completely elucidated, and we therefore adopted a systems pharmacology modeling approach to gain understanding of the effect of p75 on the dynamics of NGF signal transduction. Specifically, models were developed for the so-called heterodimer and for the ligand-passing hypotheses. We used the model to compare the effect of inhibition of NGF and TrkA and its implication for drug discovery and development for pain treatment.
CPT Pharmacometrics Syst Pharmacol 2014 Dec 03
PMID:Systems Pharmacology of the NGF Signaling Through p75 and TrkA Receptors. 2547 Jan 84