University of California, San Diego, Department of Medicine, Division of Nephrology-Hypertension, the Stein Institute for Research on Aging, and the Veterans Administration San Diego Healthcare System, San Diego, California 92161, USA
Address for correspondence: Joseph Satriano, UCSD and VASDHS, 3350 La Jolla Village Dr. (9111H), San Diego, CA 92161, USA. Voice: 858-552-8585 x6167; fax: 858-552-7549. e-mail: jsatriano{at}ucsd.edu
Ann. N.Y. Acad. Sci. 1009: 34-43 (2003).
In acute inflammatory responses, such as wound healing and glomerulonephritis,
arginine is the precursor for production of the cytostatic molecule
nitric oxide (NO) and the pro-proliferative polyamines. NO is
an early phase response whereas increased generation of polyamines
is requisite for the later, repair phase response. The temporal
switch of arginine as a substrate for the inducible nitric oxide
synthase (iNOS)/NO axis to arginase/ornithine decarboxylase
(ODC)/polyamine axis is subject to regulation by inflammatory
cytokines as well as interregulation by the arginine metabolites
themselves. Herein we describe the capacity of another arginine
pathway, the metabolism of arginine to agmatine by arginine
decarboxylase (ADC), to aid in this interregulation. Agmatine
is an antiproliferative molecule due to its suppressive effects
on intracellular polyamine levels, whereas the aldehyde metabolite
of agmatine is a potent inhibitor of iNOS. We propose that the
catabolism of agmatine to its aldehyde metabolite may act as
a gating mechanism at the transition from the iNOS/NO axis to
the arginase/ODC/polyamine axis. Thus, agmatine has the potential
to serve in the coordination of the early and repair phase pathways
of arginine in inflammation.
