Venturini G, Colasanti M, Ascenzi P
Department of Biology, Third University of Rome, Italy.
Biochem Biophys Res Commun. 1998 Aug 10;249(1):263-5. doi: 10.1006/bbrc.1998.9123.
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 Ki values of 5.0 x 10(-5) M and 7.8 x 10(-5) M, respectively, at pH 7.5 and 37.0 degrees 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 beta-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.
