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

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.

SUBMITTER: Banjarnahor S

PROVIDER: S-EPMC9217908 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature

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

Banjarnahor Sofna S König Jörg J Maas Renke R

Amino acids 20220404 7

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 effe ...[more]

PMID: 35377022

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Project description:BACKGROUND:The differential effects of commonly prescribed combined antiretroviral therapy (cART) regimens on AIDS-defining neurological conditions (neuroAIDS) remain unknown. SETTING:Prospective cohort studies of HIV-positive individuals from Europe and the Americas included in the HIV-CAUSAL Collaboration. METHODS:Individuals who initiated a first-line cART regimen in 2004 or later containing a nucleoside reverse transcriptase inhibitor backbone and either atazanavir, lopinavir, darunavir, or efavirenz were followed from cART initiation until death, lost to follow-up, pregnancy, the cohort-specific administrative end of follow-up, or the event of interest, whichever occurred earliest. We evaluated 4 neuroAIDS conditions: HIV dementia and the opportunistic infections toxoplasmosis, cryptococcal meningitis, and progressive multifocal leukoencephalopathy. For each outcome, we estimated hazard ratios for atazanavir, lopinavir, and darunavir compared with efavirenz via a pooled logistic model. Our models were adjusted for baseline demographic and clinical characteristics. RESULTS:Twenty six thousand one hundred seventy-two individuals initiated efavirenz, 5858 initiated atazanavir, 8479 initiated lopinavir, and 4799 initiated darunavir. Compared with efavirenz, the adjusted HIV dementia hazard ratios (95% confidence intervals) were 1.72 (1.00 to 2.96) for atazanavir, 2.21 (1.38 to 3.54) for lopinavir, and 1.41 (0.61 to 3.24) for darunavir. The respective hazard ratios (95% confidence intervals) for the combined end point were 1.18 (0.74 to 1.88) for atazanavir, 1.61 (1.14 to 2.27) for lopinavir, and 1.36 (0.74 to 2.48) for darunavir. The results varied in subsets defined by calendar year, nucleoside reverse transcriptase inhibitor backbone, and age. CONCLUSION:Our results are consistent with an increased risk of neuroAIDS after initiating lopinavir compared with efavirenz, but temporal changes in prescribing trends and confounding by indication could explain our findings.

Dataset Information

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

Publications

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

Similar Datasets

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