Naphthoquinones and bioactive compounds from tobacco as modulators of neuronal nitric oxide synthase activity.
Studies were conducted with extracts of several varieties of tobacco in search of neuronal nitric oxide synthase (nNOS) inhibitors which may be of value in the treatment of stroke. Current therapies do not directly exploit modulation of nNOS activity due to poor selectivity of the currently available nNOS inhibitors. The properties of a potentially novel nNOS inhibitor(s) derived from tobacco extracts, and the concentration-dependent, modulatory effects of the tobacco-derived naphthoquinone compound, 2,3,6-trimethyl-1,4-naphthoquinone (TMN), on nNOS activity were investigated, using 2-methyl-1,4-naphthoquinone (menadione) as a control. Up to 31 microM, both TMN and menadione stimulated nNOS-catalysed L-citrulline production. However, at higher concentrations of TMN (62.5-500 microM), the stimulation was lost in a concentration-dependent manner. With TMN, the loss of stimulation did not decrease beyond the control activity. With menadione (62.5-500 microM), the loss of stimulation surpassed that of the control (78+/-0.01% of control activity), indicating a true inhibition of nNOS activity. This study suggests that potential nNOS inhibitors are present in tobacco, most of which remain to be identified.
Department of Biological Sciences, University of Texas at El Paso, El Paso, TX 79968, USA.
Priya
P
Venkatakrishnan
C Gary
CG
Gairola
Neal
N
Castagnoli
R Timothy
RT
Miller
D002851:Chromatography, High Pressure Liquid; D002956:Citrulline / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000302:isolation & purification / Q000494:pharmacology*; D009249:NADP / Q000378:metabolism; D009285:Naphthoquinones / Q000302:isolation & purification / Q000494:pharmacology*; D052248:Nitric Oxide Synthase Type I / Q000037:antagonists & inhibitors*; D010084:Oxidation-Reduction; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D014026:Nicotiana / Q000737:chemistry*; D024483:Vitamin K 3 / Q000494:pharmacology
C432524:2,3,6-trimethyl-1,4-naphthoquinone; D004791:Enzyme Inhibitors; D009285:Naphthoquinones; D010936:Plant Extracts; D002956:Citrulline; D009249:NADP; D024483:Vitamin K 3; D052248:Nitric Oxide Synthase Type I