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Amidative peptide processing and vascular function

C D Oldham1, C Li, J Feng

  • 1School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta 30332, USA.

The American Journal of Physiology
|January 22, 1998
PubMed
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The precursor to Substance P (SP), SP-Gly, relaxes blood vessels by activating nitric oxide synthase (NOS). This process requires amidative processing, highlighting its role in basal endothelial cell NOS activity and vasodilation.

Area of Science:

  • Cardiovascular Physiology
  • Endocrinology
  • Biochemistry

Background:

  • Substance P (SP), a sensory nerve peptide, influences cardiovascular function.
  • Exogenous SP activates nitric oxide synthase (NOS) in endothelial cells, impacting vasodilation.

Purpose of the Study:

  • To investigate the role of SP-Gly, the precursor to SP, in vasodilation.
  • To determine if amidative processing is essential for SP-Gly's vasodilatory effects and NOS activation.

Main Methods:

  • Vascular relaxation assays using rat aortic strips.
  • Treatment with 4-phenyl-3-butenoic acid (PBA), an amidating enzyme inhibitor.
  • Measurement of endothelial cell nitric oxide synthase (NOS) activity.
  • Affinity chromatography and Western blot analysis for amidating enzymes.

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Main Results:

  • SP-Gly induced vasodilation comparable to SP.
  • PBA inhibited SP-Gly's vasodilatory effect but not SP's, indicating a requirement for amidative processing.
  • PBA decreased basal NOS activity in endothelial cells without causing cell death or directly inhibiting NOS.
  • Endothelial cells possess both bifunctional and monofunctional amidating enzymes.

Conclusions:

  • Amidative processing of SP-Gly is crucial for its vasodilatory action.
  • This processing pathway is linked to NOS activation in endothelial cells.
  • Products of amidative processing contribute to the basal activation of NOS in endothelial cells, influencing cardiovascular function.