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Assessment of Mitochondrial Functions and Cell Viability in Renal Cells Overexpressing Protein Kinase C Isozymes
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Extracellular ATP and bradykinin increase cGMP in vascular endothelial cells via activation of PKC

A F Castro1, C Amorena, A Müller

  • 1Instituto de Investigaciones Cardiológicas, Facultad de Medicina, Universidad de Buenos Aires, 1122 Buenos Aires, Argentina.

The American Journal of Physiology
|August 5, 1998
PubMed

Insights

Endothelium-dependent vasodilation involves nitric oxide (NO) and cyclic guanosine monophosphate (cGMP). This study shows protein kinase C (PKC) activation is crucial for ATP and bradykinin to increase cGMP levels in endothelial cells.

Area of Science:

  • Vascular Biology
  • Cell Signaling
  • Biochemistry

Background:

  • Vasodilation relies on nitric oxide (NO), the endothelium-dependent relaxing factor (EDRF).
  • EDRF release elevates cyclic guanosine monophosphate (cGMP) in endothelial and smooth muscle cells.
  • The precise signaling pathway for cGMP increases remains unclear.

Purpose of the Study:

  • To investigate the role of protein kinase C (PKC) in cGMP elevation induced by ATP and bradykinin.
  • To elucidate the signaling mechanisms linking EDRF agonists to cGMP production in endothelial cells.

Main Methods:

  • Cultured porcine aortic endothelial cells were used.
  • PKC activity was measured via substrate phosphorylation.
  • cGMP levels were quantified using radioimmunoassay.

Main Results:

  • Extracellular ATP and bradykinin simultaneously increased cGMP levels and PKC activity.
  • PKC inhibitors (staurosporine, calphostin C, Cremophor EL) blocked ATP-induced cGMP elevation and reduced bradykinin-induced elevation.
  • PKC activator (phorbol 12-myristate 13-acetate) elevated cGMP levels.

Conclusions:

  • EDRF agonists elevate cGMP in endothelial cells through PKC stimulation.
  • PKC plays a significant role in the signaling pathway of EDRF-mediated vasodilation.

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