Organic anion transporter 2 (SLC22A7) is a facilitative transporter of cGMP

Cheryl D. Cropp, Takafumi Komori, James E. Shima, Thomas J. Urban, Wah Yee Sook, Swati S. More, Kathleen M. Giacomini

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73 Scopus citations

Abstract

The second messenger, cGMP, mediates a host of cellular responses to various stimuli, resulting in the regulation of many critical physiologic functions. The existence of specific cGMP transporters on the plasma membrane that participate in the regulation of cGMP levels has been suggested in a large number of studies. In this study, we identified a novel plasma membrane transporter for cGMP. In particular, we showed that hOAT2 (SLC22A7), a member of the solute carrier (SLC) superfamily, was a facilitative transporter for cGMP and other guanine nucleotides. hOAT2, which is ubiquitously expressed at high levels in many cell types, was previously thought to primarily transport organic anions. Among purine and pyrimidine nucleobases, nucleosides, and nucleotides, hOAT2 showed the greatest preference for cGMP, which transported cGMP with a Km value of 88 ± 11 μM and exhibited between 50- and 100-fold enhanced uptake over control cells. Our data revealed that hOAT2 is a bidirectional facilitative transporter that can control both intracellular and extracellular levels of cGMP. In addition, we observed that a common alternatively spliced variant of hOAT2 demonstrated a complete loss of transport function as a result of a low expression level on the plasma membrane. We conclude that hOAT2 is a highly efficient, facilitative transporter of cGMP and may be involved in cGMP signaling in many tissues. Our study suggests that hOAT2 represents a potential new drug target for regulating cGMP levels.

Original languageEnglish (US)
Pages (from-to)1151-1158
Number of pages8
JournalMolecular Pharmacology
Volume73
Issue number4
DOIs
StatePublished - Apr 2008

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    Cropp, C. D., Komori, T., Shima, J. E., Urban, T. J., Sook, W. Y., More, S. S., & Giacomini, K. M. (2008). Organic anion transporter 2 (SLC22A7) is a facilitative transporter of cGMP. Molecular Pharmacology, 73(4), 1151-1158. https://doi.org/10.1124/mol.107.043117