Recent advances in studies of SLCO2A1 as a key regulator of the delivery of prostaglandins to their sites of action

Takeo Nakanishi, Yoshinobu Nakamura, Junji Umeno

研究成果: ジャーナルへの寄稿総説査読

9 被引用数 (Scopus)

抄録

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, PGF, 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.

本文言語英語
論文番号107803
ジャーナルPharmacology and Therapeutics
223
DOI
出版ステータス出版済み - 7月 2021

!!!All Science Journal Classification (ASJC) codes

  • 薬理学
  • 薬理学(医学)

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