XXXX -releasing action of @entity10696 : analysis of its action site using sepiapterin.

@entity24268 @entity8083 @entity935 @entity2340 @entity9191 @entity8490 @entity1154 @entity10696 @entity35 @entity842 @entity669
Recently, we reported that @entity10696 ( @entity8083 ), a natural cofactor for hydroxylases of @entity669 and @entity2340 , has a @entity1154 -releasing action independent of its cofactor activity. Here we attempted to determine whether 6R-BH4 acts inside the cell or from the outside of the cell by using brain microdialysis in the @entity35 striatum. For this purpose, sepiapterin, and immediate precursor of 6R-BH4 in the salvage pathway, was used to selectively increase the intracellular 6R-BH4 levels. Dialytic perfusion of sepiapterin increased tissue levels of reduced biopterin (mainly 6R-BH4) but not the extracellular levels. Administration of @entity24268 increased the extracellular levels of @entity9191 ( @entity9191 ) (an index of in vivo @entity669 hydroxylase activity) and of @entity935 (DA) (an index of in vivo DA release). Either of the increases was eliminated after pretreatment with a @entity669 hydroxylase inhibitor @entity8490 . Administration of 6R-BH4 increased extracellular levels of reduced biopterin. @entity9191 , and DA. After pretreatment with @entity8490 , the increase in @entity9191 levels was abolished, but most of the increase in DA levels persisted. The increase in DA levels also persisted after pretreatment with @entity842 synthase inhibitors. These data demonstrate that 6R-BH4 stimulates DA release directly, independent of its cofactor action for @entity669 hydroxylase and @entity842 synthase, by acting from the outside of neurons.
