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Abstract
A large number of substances of medical importance have been isolated from marine
flora and fauna and their chemical structures were elucidated. Among the many compounds
isolated in our laboratories only two compounds were identified as neurotoxins as
they produced depolarizing effects in nerve fibers. The Xestospongin D and Araguspongin
C, isolated and purified to 100% from sponge, Haliclona exigua were tested for their
effects on rat brain nitric oxide synthase (NOS) activity in vitro. The results showed
that NOS activity was significantly inhibited in a concentration and time dependent
manner with an estimated IC50 of 31.5 and 46.5 microM for Xestospongin D and Araguspongin
C, respectively, and the maximum inhibition occurred within 3 min of incubation. To
explore the mechanism of action of these compounds on NOS, we have conducted kinetic
studies with L-arginine, NADPH and Ca2+ in the presence of IC50 concentrations of
these two compounds. The maximum velocity (Vmax) and enzyme constant (Km) were calculated
using the Michaelis Menten equation. The results show that both compounds are competitive
inhibitors of NOS with the substrate, L-arginine and uncompetitive with NADPH and
free Ca2+. The NOS inhibition by these two compounds was similar to N omega-nitro-L-arginine
methylester (L-NAME), a known inhibitor of NOS. These results suggest that the marine
biomolecules Xestospongin D and Araguspongin C are in vitro modulators of neuronal
NOS.