GAMMA-GLUTAMYL DOPA - KIDNEY-SPECIFIC DOPAMINE PRECURSOR

  • 1 January 1978
    • journal article
    • research article
    • Vol. 206  (1) , 227-232
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-dihydroxyphenyalanine (.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 [EC 2.3.2.2] and aromatic L-amino acid decarboxylase, 2 enzymes which were 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 per 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 are slight. The pro-drug .gamma.-glutamyl dopa can be used as a specific renal vasodilator.