gamma-Glutamyl dopa: a kidney-specific dopamine precursor

Abstract

gamma-Glutamyl derivatives of amino acids and peptides are selectively accumulated in the kidney and introduced into the metabolism of kidney cells. gamma-Glutamyl L-3,4-dihydroxyphenylalanine (gamma-glutamyl dopa) was synthesized both chemically and enzymatically. Injection of this derivative into mice led to a selective generation of dopamine in the kidney as a consequence of the sequential action of gamma-glutamyl transpeptidase and aromatic L-amino acid decarboxylase, two enzymes which are highly concentrated in the kidney. The concentration of dopamine in the kidney after gamma-glutamyl dopa was almost 5 times higher than that after an equivalent dose of L-dopa. Infusion of 10 nmol/g/30 min of gamma-glutamyl dopa to rats produced a 60% increase in renal plasma flow. By contrast the same dose of L-dopa had no effect on renal plasma flow. Only a small pressor effect was observed after the infusion dose of gamma-glutamyl dopa was increased 20-fold indicating that the systemic effects of this pro-drug slight. The results suggest that the pro-drug gamma-glutamyl dopa can be used as a specific renal vasodilator.