Detail of "36889-13-1"

Reference

Inhibition of endothelial cell amino acid transport System y+ by arginine analogs that inhibit nitric oxide synthase

Inhibition of endothelial cell amino acid transport System y+ by arginine analogs that inhibit nitric oxide synthase. McDonald, Kelly K.; Rouhani, Riaz; Handlogten, Mary E.; Block, Edward R.; Griffith, Owen W.; Allison, R. Donald; Kilberg, Michael S. ( Department of Biochemistry and Molecular Biology, University of Florida College of Medicine, Box 100245, Gainesville, FL 32610-0245, USA). Biochimica et Biophysica Acta, 1324(1), 133-141 (English) 1997 Elsevier. CODEN: BBACAQ. ISSN: 0006-3002. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) A variety of Nw-monosubstituted L-arginine analogs are established inhibitors of nitric oxide synthase; in all cases, initial binding is competitive with the substrate L-arginine. The efficacy of such compds. in vivo will depend on their transport into the relevant nitric oxide synthase-contg. cells; in fact, inhibition may actually be augmented if cellular uptake of L-arginine is also blocked by the analogs. Because vascular endothelial cells synthesize vasoactive nitric oxide under both physiol. and pathophysiol. conditions, we have performed inhibition analyses with novel arginine analogs to det. the substrate specificity of the primary L-arginine transport system, Na+-independent System y+, present in porcine pulmonary artery endothelial cells. As reported by others, no Na+-independent System bo,+ activity was detectable. For System y+, Dixon plots suggest competitive inhibition and apparent Ki values, which ranged between 0.1 and 0.8 mM, were estd. 53774-63-3 and 36889-13-1 which are cas registry numbers of substances are two of reagents here. for each inhibitor. Some influence of amino acid side chain structure could be detected, but in general, the data establish that this transport system accepts a broad range of arginine derivs. Loading the cells with individual arginine analogs resulted in trans-stimulation of arginine uptake suggesting that they serve as substrates of System y+ as well as inhibitors. These results indicate that plasma membrane transport is unlikely to be a limiting factor in drug development for nitric oxide synthase inhibitors. .