8-Nitro-cGMP modulates exocytosis in adrenal chromaffin cells

Hiroyasu Tsutsuki, Shingo Kasamatsu, Kohei Kunieda, Tomoaki Ida, Tomohiro Sawa, Nobuyuki Sasakawa, Takaaki Akaike, Hideshi Ihara

Research output: Contribution to journalArticlepeer-review

Abstract

Nitric oxide (NO)-mediated production of cyclic guanosine 3′,5′-monophosphate (cGMP) is a crucial signaling pathway that controls a wide array of neuronal functions, including exocytotic neurotransmitter release. A novel nitrated derivative of cGMP, 8-nitro-cGMP, not only activates cGMP-dependent protein kinase (PKG), but also has membrane permeability and redox activity to produce superoxide and S-guanylated protein. To date, no studies have addressed the effects of 8-nitro-cGMP on exocytotic kinetics. Here, we aimed to assess the 8-nitro-cGMP-mediated modulation of the depolarization-evoked catecholamine release from bovine chromaffin cells. 8-Nitro-cGMP was produced in bovine chromaffin cells dependent on NO donor. Amperometric analysis revealed that 8-nitro-cGMP modulated the kinetic parameters of secretory spikes from chromaffin cells, particularly decreased the speed of individual spikes, resulting in a reduced amperometric spike height, slope β, and absolute value of slope γ. The modulatory effects were independent of the PKG signal and superoxide production. This is the first study to demonstrate that 8-nitro-cGMP modulates exocytosis and provide insights into a novel regulatory mechanism of exocytosis.

Original languageEnglish
Pages (from-to)225-230
Number of pages6
JournalBiochemical and biophysical research communications
Volume526
Issue number1
DOIs
Publication statusPublished - 2020 May 21

Keywords

  • 8-Nitro-cGMP
  • Amperometry
  • Chromaffin cells
  • Exocytosis
  • Nitric oxide

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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