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Roles of Organic Anion Transporting Polypeptide 2A1 (OATP2A1/SLCO2A1) in Regulating the Pathophysiological Actions of Prostaglandins

  • Review Article
  • Theme: Roles of Transporters in Disease and Drug Therapy
  • Published:
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Abstract

Solute carrier organic anion transporter family member 2A1 (OATP2A1, encoded by the SLCO2A1 gene), which was initially identified as prostaglandin transporter (PGT), is expressed ubiquitously in tissues and mediates the distribution of prostanoids, such as PGE2, PGF2α, PGD2 and TxB2. It is well known to play a key role in the metabolic clearance of prostaglandins, which are taken up into the cell by OATP2A1 and then oxidatively inactivated by 15-ketoprostaglandin dehydrogenase (encoded by HPGD); indeed, OATP2A1-mediated uptake is the rate-limiting step of PGE2 catabolism. Consequently, since OATP2A1 activity is required for termination of prostaglandin signaling via prostanoid receptors, its inhibition can enhance such signaling. On the other hand, OATP2A1 can also function as an organic anion exchanger, mediating efflux of prostaglandins in exchange for import of anions such as lactate, and in this context, it plays a role in the release of newly synthesized prostaglandins from cells. These different functions likely operate in different compartments within the cell. OATP2A1 is reported to function at cytoplasmic vesicle/organelle membranes. As a regulator of the levels of physiologically active prostaglandins, OATP2A1 is implicated in diverse physiological and pathophysiological processes in many organs. Recently, whole exome analysis has revealed that recessive mutations in SLCO2A1 cause refractory diseases in humans, including primary hypertrophic osteoarthropathy (PHO) and chronic non-specific ulcers in small intestine (CNSU). Here, we review and summarize recent information on the molecular functions of OATP2A1 and on its physiological and pathological significance.

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Abbreviations

AEC:

Alveolar epithelial cell

CEAS:

Chronic enteropathy associated with SLCO2A1

CMUSE:

Cryptogenic multifocal ulcerous stenosing enteritis

CNSU:

Chronic non-specific ulcers in small intestine

EP:

E prostanoid receptor

HOA:

Hypertrophic osteoarthropathy

OATP:

Organic anion transporting polypeptide(s)

PHO:

Primary hypertrophic osteoarthropathy

RMIC:

Renal medullary interstitial cell

TMD:

Transmembrane domain

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Acknowledgments

This research was carried out with the support of a Grant-in-Aid for Scientific Research (KAKENHI, 15H04755) from the Japan Society for the Promotion of Science and the Smoking Research Foundation (Tokyo, Japan) to T. N. We also thank Dr. Kouichi Kawazu at Santen Pharmaceutical Co., Ltd. for technical asisitance for measuring intraocular pressure of mice. 

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  1. Department of Membrane Transport and Biopharmaceutics, Faculty of Pharmaceutical Sciences, Kanazawa University, Kakuma-machi, Kanazawa, 920-1192, Japan

    Takeo Nakanishi & Ikumi Tamai

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  1. Takeo Nakanishi
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Correspondence to Takeo Nakanishi.

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Nakanishi, T., Tamai, I. Roles of Organic Anion Transporting Polypeptide 2A1 (OATP2A1/SLCO2A1) in Regulating the Pathophysiological Actions of Prostaglandins. AAPS J 20, 13 (2018). https://doi.org/10.1208/s12248-017-0163-8

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