8-Nitro-cGMP modulates exocytosis in adrenal chromaffin cells

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 pr...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 2020-05, Vol.526 (1), p.225-230
Main Authors: Tsutsuki, Hiroyasu, Kasamatsu, Shingo, Kunieda, Kohei, Ida, Tomoaki, Sawa, Tomohiro, Sasakawa, Nobuyuki, Akaike, Takaaki, Ihara, Hideshi
Format: Article
Language:English
Subjects:
8-Nitro-cGMP
Amperometry
Chromaffin cells
Exocytosis
Nitric oxide
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Summary: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. [Display omitted] •Production of 8-nitro-cGMP in astrocytes, CGCs, and chromaffin cells is NO-dependent.•8-Nitro-cGMP reduced spike height and .|slope γ| parameters of exocytosis kinetics.•Effects of 8-nitro-cGMP on catecholamine exocytosis is concentration-dependent.•The modulatory effects were independent of PKG signal and superoxide production.
ISSN:0006-291X
1090-2104
DOI:10.1016/j.bbrc.2020.03.045