gamma-Glutamyl dopa: a kidney-specific dopamine precursor.
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.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004295:Dihydroxyphenylalanine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D005260:Female; D005971:Glutamates; D007668:Kidney / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism*; D007980:Levodopa / Q000378:metabolism / Q000494:pharmacology; D008297:Male; D051379:Mice; D051381:Rats; D012039:Regional Blood Flow / Q000187:drug effects
D005971:Glutamates; D007980:Levodopa; D004295:Dihydroxyphenylalanine; D004298:Dopamine