Aprotinin, the first competitive protein inhibitor of NOS activity

Giorgio Venturini, Marco Colasanti, Paolo Ascenzi

Research output: Contribution to journalArticlepeer-review


Analogs of L-arginine represent the largest and potentially most useful class of NOS inhibitors. However, no competitive protein inhibitors of NOS activity are known so far. The effect of aprotinin (Kunitz inhibitor) on NOS activity is reported here, aprotinin being one of the most extensively studied globular proteins. Present data indicate that aprotinin, clinically used as a trypsin-like serine proteinase inhibitor, inhibits NOS-I and NOS-II with K(i) values of 5.0 x 10-5 M and 7.8 x 10-5 M, respectively, at pH 7.5 and 37.O°C, thereby representing the first competitive protein inhibitor of NOS activity. Therefore, the clinical use of aprotinin, as a drug, should be under careful control. In addition, aprotinin and aprotinin-like domains are present in a variety of organs, as well as in the Alzheimer's amyloid β-protein precursor. Thus, the present findings open the way to novel mechanisms likely to be involved in the modulation of NOS activity, under physiological and pathological conditions.

Original languageEnglish
Pages (from-to)263-265
Number of pages3
JournalBiochemical and Biophysical Research Communications
Issue number1
Publication statusPublished - Aug 10 1998


  • Aprotinin
  • Nitric oxide synthase inhibition
  • Rat brain constitutive nitric oxide synthase
  • Rat lung inducible nitric oxide synthase

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

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