THE RENAL HANDLING OF DOPAMINE ORIGINATING FROM L-DOPA AND GAMMA-GLUTAMYL-L-DOPA

I The formation and outflow of dopamine and its deaminated metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) was studied in cortical fragmen ts of the rat kidney loaded with L-beta-3,4-dihydroxyphenylalanine (L- DOPA) or gamma-glutamyl-L-DOPA (GluDOPA). Dopamine and DOPAC in the ti ssues and in the effluent were assayed by means of h.p.l.c. with elect rochemical detection. 2 In rats given 30 mg kg(-1) L-DOPA, tissue and outflow levels of both dopamine and DOPAC were 3 fold those observed w ith a lower dose of L-DOPA (IO mg kg(-1)). In rats given GluDOPA (16.7 mg kg(-1)) levels of dopamine in renal tissues and in perifusate samp les were found to be higher than those obtained with an equimolar dose of L-DOPA. (10 mg kg(-1)); however, no significant difference was obs erved for DOPAC. The outflow of both dopamine and DOPAC in kidney slic es of rats injected with L-DOPA (10 and 30 mg kg(-1)) or GluDOPA (16.7 mg kg(-1)) was found to decline monophasically with similar slopes of decline. The rate constants of loss (k, min(-1)) of DOPAC (10 mg kg(- 1) L-DOPA, k = 0.0070; 30 mg kg(-1) L-DOPA, k = 0.0087; 16.7 mg kg(-1) GluDOPA, k = 0.0080) were 2 to 3 fold those of dopamine (10 mg kg(-1) L-DOPA, k = 0.0027; 30 mg kg(-1) L-DOPA, k = 0.0034; 16.7 mg kg(-1) G luDOPA, k = 0.0030). With both precursors the DOPAC/dopamine ratio in perifusate samples were 2.0 fold those in the tissues. 3 Tissue and ou tflow levels of dopamine after incubation of renal tissues with L-DOPA , 50 and 100 mu M were found to be lower than those observed with GluD OPA (50 and 100 mu M). DOPAC/dopamine ratios in tissues and perifusate samples of experiments performed with L-DOPA were significantly highe r (P < 0.01) than those observed with GluDOPA. The outflow of both dop amine and DOPAC in renal slices incubated with L-DOPA (50 and 100 mu M ) were found to decline with time, but presented a biphasic shape. DOP AC/dopamine ratios in perifusate samples were 3 fold that in the tissu es with both precursors. 4 In conclusion, the present results show tha t both L-DOPA and GluDOPA give origin to substantial amounts of dopami ne and the newly-formed amine undergoes considerable deamination to DO PAC. However, dopamine originating from GluDOPA was less deaminated th an that resulting from L-DOPA; it appears that this different behaviou r may concern aspects related to the formation of the amine and also t hose related to its deamination and disposition, namely the processes involved in the access of newly-formed dopamine to MAO.