Kidney as a site of uptake and metabolism of gamma-glutamyl compounds.

gamma-Glutamyl derivatives of amino acids are extensively metabolized and accumulated in the kidney. The kideny also has a high capacity to synthesize ophthalmic acid, an analog of glutathione. These processes can be attributed to the high activity in the kidney of enzymes that both degrade and synthesize glutathione. Th possibility of using the gamma-glutamyl group as a carrier for the introduction of compounds containing an amino function into kidney metabolism was explored. Administration of L-gamma-glutamyl-L-3,4-di-hydroxyphenylalanine (gamma-glutamyl-DOPA) to rats led to the accumulation of gamma-glutamyl-DOPA in the kidney, release of DOPA and its conversion to dopamine by the action of aromatic amino acid decarboxylase. Dopamine actively generated in the kidney increased renal plasma flow and sodium excretion. No systemic effects or untoward reactions attributable to this amine were observed. It is suggested that gamma-glutamyl derivatives of certain drugs may be useful as kidney specific prodrugs.