2021年1月
Recent advances in studies of SLCO2A1 as a key regulator of the delivery of prostaglandins to their sites of action
Pharmacology & Therapeutics
- ,
- ,
- 巻
- 223
- 号
- 開始ページ
- 107803
- 終了ページ
- 107803
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1016/j.pharmthera.2021.107803
- 出版者・発行元
- Elsevier BV
Solute carrier organic anion transporter family member 2A1 (SLCO2A1, also known as PGT, OATP2A1, PHOAR2, or SLC21A2) is a plasma membrane transporter consisting of 12 transmembrane domains. It is ubiquitously expressed in tissues, and mediates the membrane transport of prostaglandins (PGs, mainly PGE2, PGF2α, PGD2) and thromboxanes (e.g., TxB2). SLCO2A1-mediated transport is electrogenic and is facilitated by an outwardly directed gradient of lactate. PGs imported by SLCO2A1 are rapidly oxidized by cytoplasmic 15-hydroxyprostaglandin dehydrogenase (15-PGDH, encoded by HPGD). Accumulated evidence suggests that SLCO2A1 plays critical roles in many physiological processes in mammals, and it is considered a potential pharmacological target for diabetic foot ulcer treatment, antipyresis, and non-hormonal contraception. Furthermore, whole-exome analyses suggest that recessive inheritance of SLCO2A1 mutations is associated with two refractory diseases, primary hypertrophic osteoarthropathy (PHO) and chronic enteropathy associated with SLCO2A1 (CEAS). Intriguingly, SLCO2A1 is also a key component of the Maxi-Cl channel, which regulates fluxes of inorganic and organic anions, including ATP. Further study of the bimodal function of SLCO2A1 as a transporter and ion channel is expected to throw new light on the complex pathology of human diseases. Here, we review and summarize recent information on the molecular functions of SLCO2A1, and we discuss its pathophysiological significance.
- リンク情報
- ID情報
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- DOI : 10.1016/j.pharmthera.2021.107803
- ISSN : 0163-7258
- PubMed ID : 33465398