NYMC Faculty Publications

PGF2alpha Regulates the Basolateral K Channels in the Distal Convoluted Tubule

DOI

10.1152/ajprenal.00102.2017

Journal Title

American Journal of Physiology.Renal Physiology

First Page

F254

Last Page

F261

Document Type

Article

Publication Date

August 2017

Department

Pharmacology

Abstract

Our aim is to examine the role of PGF2alpha receptor (FP), a highly expressed prostaglandin receptor in the distal convoluted tubule (DCT) in regulating the basolateral 40-pS K channel. The single-channel studies demonstrated that PGF2alpha had a biphasic effect on the 40-pS K channel in the DCT-PGF2alpha stimulated at low concentrations (less than 500 nM), while at high concentrations (above 1 microM), it inhibited the 40-pS K channels. Moreover, neither 13,14-dihydro-15-keto-PGF2alpha (a metabolite of PGF2alpha) nor PGE2 was able to mimic the effect of PGF2alpha on the 40-pS K channel in the DCT. The inhibition of PKC had no significant effect on the 40-pS K channel; however, it abrogated the inhibitory effect of 5 microM PGF2alpha on the K channel. Moreover, stimulation of PKC inhibited the 40-pS K channel in the DCT, suggesting that PKC mediates the inhibitory effect of PGF2alpha on the 40-pS K channel. Conversely, the stimulatory effect of PGF2alpha on the 40-pS K channel was absent in the DCT treated with DPI, a NADPH oxidase (NOX) inhibitor. Also, adding 100 microM H2O2 mimicked the stimulatory effect of PGF2alpha and increased the 40-pS K channel activity in DCT. Moreover, the stimulatory effect of 500 nM PGF2alpha and H2O2 was not additive, suggesting the role of superoxide-related species in mediating the stimulatory effect of PGF2alpha on the 40-pS K channel. The inhibition of Src family tyrosine protein kinase (SFK) not only inhibited the 40-pS K channel in the DCT but also completely abolished the stimulatory effects of PGF2alpha and H2O2 on the 40-pS K channel. We conclude that PGF2alpha at low doses stimulates the basolateral 40-pS K channel by a NOX- and SFK-dependent mechanism, while at high concentrations, it inhibits the K channel by a PKC-dependent pathway.

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