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BioAssay: AID 269129

Permeability across GH3 cell membrane

Nitric oxide (NO) is critical for the normal physiological regulation of the nervous system and other tissues. L-Arginine, but not D-arginine, is the natural substrate for nitric oxide synthase (NOS), for it is enzymatically converted to NO and L-citrulline. However, recent evidence suggests that D-arginine can also produce NO and NO-derivatives via a different pathway. The aim of the present more ..
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 Tested Compounds
 Tested Compounds
All(3)
 
 
Unspecified(3)
 
 
 Tested Substances
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Unspecified(3)
 
 
 Related BioAssays
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AID: 269129
Data Source: ChEMBL (382662)
Depositor Category: Literature, Extracted
BioAssay Version:
Deposit Date: 2010-05-25
Modify Date: 2014-05-22

Data Table ( Complete ):           View All Data
Tested Compounds:
Description:
Title: Galactosyl derivatives of L-arginine and D-arginine: synthesis, stability, cell permeation, and nitric oxide production in pituitary GH3 cells.

Abstract: Nitric oxide (NO) is critical for the normal physiological regulation of the nervous system and other tissues. L-Arginine, but not D-arginine, is the natural substrate for nitric oxide synthase (NOS), for it is enzymatically converted to NO and L-citrulline. However, recent evidence suggests that D-arginine can also produce NO and NO-derivatives via a different pathway. The aim of the present paper was to raise NO levels in the cells by increasing the cell permeation of its precursors. To this aim, two galactosyl prodrugs, L-arginine-D-galactos-6'-yl ester (L-ArgGal) and D-arginine-D-galactos-6'-yl ester (D-ArgGal) were synthesized. Remarkably, using the HPLC-ESI/MS technique, we found that L-ArgGal and D-ArgGal prodrugs both increased the concentration levels of L- and D-arginine and their derivatives in pituitary GH3 cells. Furthermore, we found that D-ArgGal (1) penetrated cell membranes more rapidly than its precursor D-arginine, (2) released arginine more slowly and in greater amounts than L-ArgGal, and (3) produced much higher levels of DAF-2 monitored NO and nitrite than did L-ArgGal under the same experimental conditions. In conclusion, these results indicate that an increase in the cell permeation of L- and D-arginine by L-ArgGal and D-ArgGal can lead to an increase in NO levels.
(PMID: 16884294)
Comment
Putative Target:
ChEMBL Target ID: 80141
Target Type: CELL-LINE
Cell Line: GH3
Tissue: Pituitary adenoma cells
Pref Name: GH3
Organism: Rattus norvegicus
Tax ID: 10116
Confidence: Target assigned is non-molecular
Relationship Type: Non-molecular target assigned
Categorized Comment - additional comments and annotations
From ChEMBL:
Assay Type: ADME
Assay Data Source: Scientific Literature
BAO: Assay Format: cell-based format
Assay Cell Type: GH3
Result Definitions
TIDNameDescriptionHistogramTypeUnit
OutcomeThe BioAssay activity outcomeOutcome
1permeability activity commentpermeability activity commentString
2permeability standard flagpermeability standard flagInteger
3permeability qualifierpermeability qualifierString
4permeability published valuepermeability published valueFloat
5permeability standard valuepermeability standard valueFloat

Data Table (Concise)
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