RT Journal Article
SR Electronic
T1 Isoform-specific biotransformation of glyceryl trinitrate by rat aortic glutathione S-transferases.
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 1527
OP 1534
VO 279
IS 3
A1 R Nigam
A1 D J Anderson
A1 S F Lee
A1 B M Bennett
YR 1996
UL http://jpet.aspetjournals.org/content/279/3/1527.abstract
AB The objective of this study was to purify and characterize rat aortic glutathione S-transferases (GSTs) and to assess their role in the biotransformation of the nitrovasodilator, glyceryl trinitrate (GTN). Two class alpha GSTs (Ya and Yc) a class mu GST (Yb2) and a class pi GST (Yp) were identified in rat aortic cytosol. Partial purification of three of these (Yb2, Yc and Yp) was achieved by affinity chromatography with S-hexylglutathione agarose. Further purification by cation- and anion-exchange chromatography resulted in the purification of GST Yc and GST Yb2/Yp to apparent homogeneity, a purification of 200- and 110-fold, respectively. Purified GST Yc and Yb2/Yp mediated GTN biotransformation with similar rates. GST activity and GTN biotransformation by rat aortic cytosol and affinity-purified GSTs were highly sensitive to inhibition by the class mu selective inhibitors Basilen Blue and bromosulfophthalein. Removal of GST Yb2 from rat aortic cytosol by immunoprecipitation resulted in marked inhibition of GST activity and GTN biotransformation. We conclude that the GSTs account for the major portion of GTN biotransformation in rat aortic cytosol, and that this is primarily attributable to the GST Yb2 isoform.