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Measurement of Cyclic Guanosine Monophosphate (cGMP) in Solid Tissues using Competitive Enzyme-Linked Immunosorbent Assay (ELISA)
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Measurement of Cyclic Guanosine Monophosphate (cGMP) in Solid Tissues using Competitive Enzyme-Linked Immunosorbent Assay (ELISA)

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The organic cation transporters rOCT1 and hOCT2 are inhibited by cGMP

E Schlatter1, V Mönnich, I Cetinkaya

  • 1Universitätsklinikum Münster, Medizinische Klinik und Poliklinik D, Experimentelle Nephrologie, Domagkstr. 3a, D-48149 Münster, Germany. eberhard.schlatter@uni-muenster.de

The Journal of Membrane Biology
|October 24, 2002
PubMed

Insights

Cyclic guanosine monophosphate (cGMP) inhibits organic cation transporters OCT1 and OCT2 in kidney cells. This inhibition is likely mediated by an intracellular mammalian cGMP-binding protein, not a direct interaction with the transporters.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Physiology

Background:

  • The organic cation transporters OCT1 and OCT2 are crucial for secreting organic cations in renal proximal tubules.
  • Previous research indicated protein kinase C modulates rat OCT1 (rOCT1) activity and selectivity.

Purpose of the Study:

  • To investigate the effect of cyclic guanosine monophosphate (cGMP) on cation transport mediated by rOCT1 and human OCT2 (hOCT2).
  • To elucidate the mechanism of cGMP's action on these transporters in different expression systems.

Main Methods:

  • Expressed rOCT1 and hOCT2 in human embryonic kidney (HEK293) cells and Xenopus laevis oocytes.
  • Measured cation uptake using fluorescent substrate ASP+ in HEK293 cells and radiolabeled cations in oocytes.
  • Assessed membrane potential changes (Vm) using patch-clamp electrophysiology in HEK293 cells.

Main Results:

  • 8-Br-cGMP significantly reduced ASP+ uptake by rOCT1-expressing HEK293 cells (up to 78% inhibition, IC50 = 24 ± 16 mM).
  • This inhibition was independent of cGMP-dependent protein kinase (PKG) and occurred intracellularly.
  • cGMP did not directly interact with rOCT1 in Xenopus oocytes, suggesting involvement of an intermediary protein.

Conclusions:

  • cGMP inhibits OCT1 and OCT2 transporter function in renal proximal tubule cells.
  • The inhibitory effect is likely mediated by a mammalian cGMP-binding protein interacting with OCT1-2.
  • This finding provides new insights into the regulation of organic cation secretion in the kidney.

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