Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Jul;54(7):1101-1108.
doi: 10.1007/s00726-022-03156-2. Epub 2022 Apr 4.

Screening of commonly prescribed drugs for effects on the CAT1-mediated transport of L-arginine and arginine derivatives

Sofna Banjarnahor  1   2 , Jörg König  1 , Renke Maas  3
Affiliations

Screening of commonly prescribed drugs for effects on the CAT1-mediated transport of L-arginine and arginine derivatives

Sofna Banjarnahor et al. Amino Acids. 2022 Jul.

Abstract

The cationic amino acid transporter 1 (CAT1/SLC7A1) plays a key role in the cellular uptake or export of L-arginine and some of its derivatives. This study investigated the effect of 113 chemically diverse and commonly used drugs (at 20 and 200 µM) on the CAT1-mediated cellular uptake of L-arginine, L-homoarginine, and asymmetric dimethylarginine (ADMA). Twenty-three (20%) of the tested substances showed weak inhibitory or stimulatory effects, but only verapamil showed consistent inhibitory effects on CAT1-mediated transport of all tested substrates.

Keywords: ADMA; CAT1; Inhibition; L-Arginine; L-Homoarginine.

PubMed Disclaimer

Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Fig. 1
Fig. 1
Inhibition of CAT1-mediated uptake of l-arginine (100 μM) in a screen of 113 commonly used drugs at A 20 μM and B 200 μM (excluding rifampicin). Each bar represents the effect of one compound on CAT1-mediated l-arginine (100 μM) uptake as percent inhibition. Data were obtained from at least two independent experiments performed in triplicate (n = 6–9) and each test data from the independent experiment were normalized to the respective control data to get the value of percent inhibition. Negative inhibition values indicate stimulated CAT1-mediated uptake. Data were analyzed using one-way ANOVA and Dunnett’s multiple comparison test with p < 0.05. Bars showing a statistically significant inhibition or transport stimulation are shaded in black
Fig. 2
Fig. 2
Inhibition of CAT1-mediated uptake of L-homoarginine (1 μM) in a screen of 113 commonly used drugs at A 20 μM and B 200 μM (excluding rifampicin). Each bar represents the effect of one compound on CAT1-mediated l-homoarginine (1 μM) uptake as percent inhibition. Data were obtained from at least two independent experiments performed in triplicate (n = 6–9) and each test data from the independent experiment were normalized to the respective control data to get the value of percent inhibition. Negative inhibition values indicate stimulated CAT1-mediated uptake. Data were analyzed using one-way ANOVA and Dunnett’s multiple comparison test with p < 0.05. Bars showing a statistically significant inhibition or transport stimulation are shaded in black
Fig. 3
Fig. 3
Inhibition of CAT1-mediated uptake of ADMA (1 μM) in a screen of 113 commonly used drugs at A 20 μM and B 200 μM (excluding rifampicin). Each bar represents the effect of one compound on CAT1-mediated ADMA (1 μM) uptake as percent inhibition. Data were obtained from at least two independent experiments performed in triplicate (n = 6–9) and each test data from the independent experiment were normalized to the respective control data to get the value of percent inhibition. Negative inhibition values indicate stimulated CAT1-mediated uptake. Data were analyzed using one-way ANOVA and Dunnett’s multiple comparison test with p < 0.05. Bars showing a statistically significant inhibition or transport stimulation are shaded in black
See this image and copyright information in PMC

References

    1. Atzler D, Gore MO, Ayers CR, Choe C-u, Böger RH, Lemos JAd, McGuire DK, Schwedhelm E. Homoarginine and cardiovascular outcome in the population-based dallas heart study. Arterioscler Thromb Vasc Biol. 2014;34(11):2501–2507. doi: 10.1161/ATVBAHA.114.304398. - DOI - PubMed
    1. Banjarnahor S, Rodionov RN, König J, Maas R. Transport of L-arginine related cardiovascular risk markers. J Clin Med. 2020 doi: 10.3390/jcm9123975. - DOI - PMC - PubMed
    1. Bentur OS, Schwartz D, Chernichovski T, Ingbir M, Weinstein T, Chernin G, Schwartz IF. Estradiol augments while progesterone inhibits arginine transport in human endothelial cells through modulation of cationic amino acid transporter-1. Am J Physiol Regul Integr Comp Physiol. 2015;309(4):R421–427. doi: 10.1152/ajpregu.00532.2014. - DOI - PubMed
    1. Böger RH, Sullivan LM, Schwedhelm E, Wang TJ, Maas R, Benjamin EJ, Schulze F, Xanthakis V, Benndorf RA, Vasan RS. Plasma asymmetric dimethylarginine and incidence of cardiovascular disease and death in the community. Circulation. 2009;119(12):1592–1600. doi: 10.1161/circulationaha.108.838268. - DOI - PMC - PubMed
    1. Bogle RG, Coade SB, Moncada S, Pearson JD, Mann GE. Bradykinin and ATP stimulate L-arginine uptake and nitric oxide release in vascular endothelial cells. Biochem Biophys Res Commun. 1991;180(2):926–932. doi: 10.1016/S0006-291X(05)81154-4. - DOI - PubMed

MeSH terms

LinkOut - more resources