ReferenceID 1595
Synergistic transport of a fluorescent coumarin probe marks coumarins as pharmacological modulators of Organic anion-transporting polypeptide, OATP3A1
Biochem Pharmacol
Organic anion-transporting polypeptide 3A1 (OATP3A1) is a membrane transporter mediating the cellular uptake of various hormones such as estrone-3-sulfate, prostaglandins E1 and E2 and thyroxine. OATP3A1 is widely expres
Relationship Network
Interactive first-hop connections across herbs, ingredients, formulas, targets, diseases, symptoms, syndromes, evidence, and monographs.
Click a node to open it in a new tab
Ingredient: 1Reference: 1Links: 1
Arranging relationship network...
Record Fields
Scalar fields from the final reference record.
- Reference Id
- 1595
- Evidence Id
- 18185
- Core Evidence Id
- 18185
- Source Reference Id
- 3197
- Herb2 Reference Id
- HBREF003994
- Subject Paper Key
- HBIN021608_32991865
- Pubmed Id
- 32991865
- Doi
- 10.1016/j.bcp.2020.114250
- Paper Title
- Synergistic transport of a fluorescent coumarin probe marks coumarins as pharmacological modulators of Organic anion-transporting polypeptide, OATP3A1
- Paper Abstract
- Organic anion-transporting polypeptide 3A1 (OATP3A1) is a membrane transporter mediating the cellular uptake of various hormones such as estrone-3-sulfate, prostaglandins E1 and E2 and thyroxine. OATP3A1 is widely expressed in the human body and its presence in tissue-blood barriers, neurons and muscle cells marks it as a potential pharmacological target. Herein we demonstrate that an otherwise membrane impermeant, zwitterionic fluorescent coumarin probe, bearing a sulfonate function is a potent substrate of human OATP3A1, thus readily transported into HEK-293-OATP3A1 cells allowing functional investigation and the screen of drug interactions of the OATP3A1 transporter. At the same time, dyes lacking either the sulfonate motif or the coumarin scaffold showed a dramatic decrease in affinity or even a complete loss of transport. Furthermore, we observed a distinct inhibition/activation pattern in the OATP3A1-mediated uptake of closely related fluorescent coumarin derivatives differing only in the presence of the sulfonate moiety. Additionally, we detected a synergistic effect between one of the probes tested and the endogenous OATP substrate estrone-3-sulfate. These data, together with docking results indicate the presence of at least two cooperative substrate binding sites in OATP3A1. Besides providing the first sensitive probe for testing OATP3A1 substrate/inhibitor interactions, our results also help to understand substrate recognition and transport mechanism of the poorly characterized OATP3A1. Moreover, coumarins are good candidates for OATP3A1-targeted drug delivery and as pharmacological modulators of OATP3A1.
- Journal
- Biochem Pharmacol
- Publish Year
- 2020
- Experiment Subject
- human; hek-293-oatp3a1 cells
- Experiment Type
- Animal & Cell Experiment
- Phenotype Related
- Paper Title Cn
- Paper Title En
- Synergistic transport of a fluorescent coumarin probe marks coumarins as pharmacological modulators of Organic anion-transporting polypeptide, OATP3A1
- Bilingual Status
- semi_complete