The UDP-glucuronosyltransferases of the blood-brain barrier: their role in drug metabolism and detoxication

摘要: UDP-glucuronosyltransferases (UGTs) form a multigenic family of membrane-bound enzymes expressed in various tissues, including brain. They catalyze the formation β-D-glucuronides from structurally unrelated substances (drugs, other xenobiotics, as well endogenous compounds) by linkage glucuronic acid high energy donor, UDP-α-D-glucuronic acid. In brain, UGTs actively participate to overall protection tissue against intrusion potentially harmful lipophilic that are metabolized hydrophilic glucuronides. These metabolites generally inactive, except for important pharmacologically glucuronides such morphine-6-glucuronide. mainly endothelial cells and astrocytes blood brain barrier (BBB). also associated interfaces devoid BBB, circumventricular organ, pineal gland, pituitary gland neuro-olfactory tissues. Beside their key-role detoxication barrier, play role steady-state compounds, like steroids or dopamine (DA) function UGT isoforms 1A, 2A, 2B 3A tissues levels known present distinct but overlapping substrate specificity. The importance these enzyme species with regard toxic, physiologically relevant will be discussed.