Regulation of human organic anion transporter 4 by parathyroid hormone-related protein and protein kinase A

Peng Duan, Shanshan Li, Guofeng You You

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

Human organic anion transporter 4 (hOAT4) belongs to a family of organic anion transporters that play critical roles in the body disposition of clinically important drugs, including anti-human immunodeficiency virus therapeutics, anti-tumor drugs, antibiotics, antihypertensives, and anti-inflammatories. hOAT4 is abundantly expressed in the kidney and placenta. In the current study, we examined the regulation of hOAT4 by parathyroid hormone-related protein (PTHrP) and protein kinase A (PKA) in kidney COS-7 cells. PTHrP induced a time and concentration-dependent stimulation of hOAT4 transport activity. The stimulation of hOAT4 activity by PTHrP mainly resulted from an increased cell surface expression without a change in total cell expression of the transporter. Activation of PKA by Bt2-cAMP also resulted in a stimulation of hOAT4 activity through an increased cell surface expression of the transporter. However, PTHrP-induced stimulation of hOAT4 activity could not be prevented by treating hOAT4-expressing cells with the PKA inhibitor H89. We concluded that both PTHrP and activation of PKA stimulate hOAT4 activity through redistribution of the transporter from intracellular compartments to the cell surface. However, PTHrP regulates hOAT4 activity by mechanisms independent of PKA pathway.

Original languageEnglish (US)
Pages (from-to)322-327
Number of pages6
JournalInternational Journal of Biochemistry and Molecular Biology
Volume3
Issue number3
StatePublished - 2012

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology

Keywords

  • Drug transporter
  • Parathyroid hormone-related protein
  • Protein kinase A
  • Regulation

Fingerprint

Dive into the research topics of 'Regulation of human organic anion transporter 4 by parathyroid hormone-related protein and protein kinase A'. Together they form a unique fingerprint.

Cite this