About this pathway
Atenolol is a hydrophilic molecule which is predominantly eliminated via the kidneys unchanged, only about 5% of the atenolol is metabolized by the liver [Article:6749509]. Candidate genes that are important are transporters, plus their variants and drug-drug interactions which can influence atenolol pharmacokinetics.
In vitro studies suggest that the organic anion transporting polypeptides OATP1A2 and OATP2B1 coded for by SLCO1A2 and SLCO2B1 are responsible for atenolol intestinal uptake [Article:21039758][Article:22574741]. These transporters are located on the luminal side of small intestine enterocytes. Uptake is inhibited by orange (SLCO1A2) and apple juice (SLCO2B1)[Article:21039758][Article:22574741][Article:29124159]. Atenolol is a substrate for ABCB1 (also known as P-gp) which is responsible for efflux transport in intestinal cells [Article:26651362].
Experiments in vitro in transfected HEK cells showed atenolol is a substrate for OCT1 and OCT2 (coded for by SLC22A1 and SLC22A2), MATE1, and MATE2-K (SLC47A1 and SLC47A2), but not by OCT3 (SLC22A3), OAT1 (SLC22A6), and OAT3 (SLC22A8) [Article:26374172]. Renal uptake possibly therefore occurs via SLC22A2, and tubular secretion by SLC47A1 and SLC47A2 [Article:26374172].
Atenolol transport in the liver is not well characterized in the literature, although it has been suggested that SLC22A1, SLC47A1, and SLC47A2 are involved [Article:26374172][Article:31004787]. Atenolol is an inhibitor for SLC22A1 and SLC22A3 in transfected cells [Article:26374172].
Reactions & interactions (23)
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Catalysis
ABCB1 → Transport
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Catalysis
SLC22A1 → Transport
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Catalysis
SLC47A1 → Transport
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Catalysis
SLC47A2 → Transport
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Catalysis
ABCB1 → Transport
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Catalysis
SLC22A1 → Transport
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Catalysis
SLCO2B1 → Transport
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Catalysis
SLCO1A2 → Transport
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Catalysis
SLC47A1 → Transport
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Catalysis
ABCB1 → Transport
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Catalysis
SLC47A2 → Transport
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Catalysis
SLC22A2 → Transport
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Inhibition
apple juice → SLC22A1
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Inhibition
apple juice → SLCO2B1
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Inhibition
orange juice → SLCO1A2
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Inhibition
atenolol → SLC22A6
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Inhibition
atenolol → SLC22A8
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Transport
atenolol → atenolol
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Transport
atenolol → atenolol
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Transport
atenolol → atenolol
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Transport
atenolol → atenolol
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Transport
atenolol → atenolol
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Transport
atenolol → atenolol
Edit history (2)
- 2018-06-06 Create
- 2024-01-18 Correction SLC22A2 was removed from hepatocyte and replaced SLC22A1 on kidney. ABCB1 was added to efflux arrow from kidney and liver. Changes were made to both gpml and images.