Nitric oxide-independent inhibitory effects of L-arginineanalog NG-monomethy-L-arginine on the generation of interleukin-2 activated cytotoxic activity in humans

António, José; Spagnoli, Giulio C.; Hörig, Heidi; Groß, Thomas; Gallati, H.; Šamijai, M.; Eljuga, Damir; Turić, Marko; Harder, F.; Heberer, Michael

doi:10.1016/s0261-5614(96)80255-x

Cited by 4 publications

(1 citation statement)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Further studies will be required to elucidate the full range of ADMA/CaSR signalling in different cells and tissues. In addition to our own observations, Juretic and co-workers (Juretic et al ., 1996) have reported that the induction of IL-2 in L-NMMA treated cultured PBMC’s is not replicated by treatment with synthetic inhibitors of NOS. Further work will be needed to establish whether L-NMMA can interact with and modulation CaSR activity.…”

Section: Discussionsupporting

confidence: 83%

Asymmetric dimethylarginine positively modulates Calcium-Sensing Receptor signalling to promote lipid accumulation and adiposity

Dowsett

Duluc

Higgins

et al. 2022

Preprint

View full text Add to dashboard Cite

Irreversible methylation of arginine residues generates asymmetric dimethylarginine (ADMA). ADMA is a competitive inhibitor of nitric oxide (NO) synthase and an independent risk factor for cardiovascular disease. Plasma ADMA concentrations increase with obesity and fall following weight loss. Here, we demonstrate that ADMA drives lipid accumulation through a newly identified NO-independent pathway via the amino-acid sensitive calcium-sensing receptor (CaSR). ADMA treatment of 3T3-L1 and HepG2 cells activates mTOR signalling and upregulates a suite of lipogenic genes with an associated increase in triglyceride content. Pharmacological blockade of CaSR inhibits ADMA driven lipid accumulation and ADMA treatment potentiates CaSR signalling via both Gq and Gi/o pathways. Impairment of ADMA metabolism in adipocytes in vivo, by dimethylamine dimethylaminohydrolase-1 (DDAH1) deletion, increases visceral adiposity and adipocyte hypertrophy. This study identifies a signalling mechanism for ADMA as an endogenous ligand of the G protein-coupled receptor CaSR that potentially contributes to the impact of ADMA in cardiometabolic disease.

show abstract

Section: Discussionsupporting

confidence: 83%