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Active pharmaceutical ingredient uptake by Zebrafish (Danio rerio) Oct2 (slc22a2) transporter expressed in Xenopus laevis Oocytes

Active pharmaceutical ingredient uptake by Zebrafish (Danio rerio) Oct2 (slc22a2) transporter expressed in Xenopus laevis Oocytes
Active pharmaceutical ingredient uptake by Zebrafish (Danio rerio) Oct2 (slc22a2) transporter expressed in Xenopus laevis Oocytes

Uptake of active pharmaceutical ingredients (APIs) across the gill epithelium of fish is via either a passive or facilitated transport process, with the latter being more important at the lower concentrations more readily observed in the environment. The solute carrier (SLC) 22A family, which includes the organic cation transporter OCT2 (SLC22A2), has been shown in mammals to transport several endogenous chemicals and APIs. Zebrafish oct2 was expressed in Xenopus oocytes and the uptake of ranitidine, propranolol, and tetraethylammonium characterized. Uptake of ranitidine and propranolol was time- and concentration-dependent with a k m and V max for ranitidine of 246 µM and 45 pmol/(oocyte × min) and for propranolol of 409 µM and 190 pmol/(oocyte × min), respectively. Uptake of tetraethylammonium (TEA) was inhibited by propranolol, amantadine, and cimetidine, known to be human OCT2 substrates, but not quinidine or ranitidine. At external media pH 7 and 8 propranolol uptake was 100-fold greater than at pH 6; pH did not affect ranitidine or TEA uptake. It is likely that cation uptake is driven by the electrochemical gradient across the oocyte. Uptake kinetics parameters, such as those derived in the present study, coupled with knowledge of transporter localization and abundance and API metabolism, can help derive pharmacokinetic models. Environ Toxicol Chem 2022;41:2993-2998. © 2022 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Absorption, emerging pollutants, in vitro toxicology, pharmaceuticals
0730-7268
2993-2998
Chang, Elisabeth
8b9853ad-b8f3-4a95-8a4a-984e00e0c446
Owen, Stewart
d103e03b-bc63-4362-ad1f-70532d677b6a
Hogstrand, Christer
62ff9212-ca64-4ff0-ab6a-7eb66a2f381c
Bury, Nic
696daba0-5cc9-444c-be9a-c678808712c6
Chang, Elisabeth
8b9853ad-b8f3-4a95-8a4a-984e00e0c446
Owen, Stewart
d103e03b-bc63-4362-ad1f-70532d677b6a
Hogstrand, Christer
62ff9212-ca64-4ff0-ab6a-7eb66a2f381c
Bury, Nic
696daba0-5cc9-444c-be9a-c678808712c6

Chang, Elisabeth, Owen, Stewart, Hogstrand, Christer and Bury, Nic (2022) Active pharmaceutical ingredient uptake by Zebrafish (Danio rerio) Oct2 (slc22a2) transporter expressed in Xenopus laevis Oocytes. Environmental Toxicology and Chemistry, 41 (12), 2993-2998. (doi:10.1002/etc.5480).

Record type: Article

Abstract

Uptake of active pharmaceutical ingredients (APIs) across the gill epithelium of fish is via either a passive or facilitated transport process, with the latter being more important at the lower concentrations more readily observed in the environment. The solute carrier (SLC) 22A family, which includes the organic cation transporter OCT2 (SLC22A2), has been shown in mammals to transport several endogenous chemicals and APIs. Zebrafish oct2 was expressed in Xenopus oocytes and the uptake of ranitidine, propranolol, and tetraethylammonium characterized. Uptake of ranitidine and propranolol was time- and concentration-dependent with a k m and V max for ranitidine of 246 µM and 45 pmol/(oocyte × min) and for propranolol of 409 µM and 190 pmol/(oocyte × min), respectively. Uptake of tetraethylammonium (TEA) was inhibited by propranolol, amantadine, and cimetidine, known to be human OCT2 substrates, but not quinidine or ranitidine. At external media pH 7 and 8 propranolol uptake was 100-fold greater than at pH 6; pH did not affect ranitidine or TEA uptake. It is likely that cation uptake is driven by the electrochemical gradient across the oocyte. Uptake kinetics parameters, such as those derived in the present study, coupled with knowledge of transporter localization and abundance and API metabolism, can help derive pharmacokinetic models. Environ Toxicol Chem 2022;41:2993-2998. © 2022 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

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Enviro Toxic and Chemistry - 2022 - Chang - Active Pharmaceutical Ingredient Uptake by Zebrafish Danio rerio Oct2 - Version of Record
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e-pub ahead of print date: 14 September 2022
Published date: 1 December 2022
Additional Information: Funding Information: The present study was conducted under funding awarded to NRB from the Biotechnology and Biological Sciences Research Council (BBSRC) CASE industrial scholarship scheme (Reference No. BB/M014827/1) and the AstraZeneca Global Sustainability Research Programme. Publisher Copyright: © 2022 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.
Keywords: Absorption, emerging pollutants, in vitro toxicology, pharmaceuticals

Identifiers

Local EPrints ID: 473183
URI: http://eprints.soton.ac.uk/id/eprint/473183
ISSN: 0730-7268
PURE UUID: 4f11c6a4-faa4-4cca-8d39-ae3480f75fdb
ORCID for Nic Bury: ORCID iD orcid.org/0000-0001-6048-6338

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Date deposited: 11 Jan 2023 17:55
Last modified: 17 Mar 2024 04:14

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Contributors

Author: Elisabeth Chang
Author: Stewart Owen
Author: Christer Hogstrand
Author: Nic Bury ORCID iD

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