OUTFLOW OF DOPAMINE AND NORADRENALINE ORIGINATING FROM L-DOPA AND L-THREO-DOPS IN RAT RENAL TISSUES

1. The present study has examined the formation and outflow of newly-formed dopamine (DA) and noradrenaline (NA) in slices of the renal cortex of rats given L-beta-3,4-dihydroxyphenylalanine (L-DOPA) (10, 30 or 100 mg/kg i.p.) and L-threo-3-(3,4-dihydroxyphenyl)serine (L-DOPS) (10, 30 or 100 mg/kg i.p.), respectively. The outflow of 3,4-dihydroxyphenylacetic acid (DOPAC) and 3,4-dihydroxyphenylglycol (DOPEG), the deaminated metabolites of DA and NA, respectively, was also measured. 2. The accumulation of both newly-formed DA and DOPAC in renal tissues after the administration of L-DOPA was found to be dose dependent; after 30 or 100 mg/kg L-DOPA, the levels of both DA and DOPAC were, respectively, 3- and 20-fold those observed after the administration of 10 mg/kg L-DOPA. The outflow of DA and DOPAC in kidney slices of rats treated with L-DOPA was found to progressively decline with time and reflected the DA and DOPAC tissue contents. The rate constant (k)for DOPAC efflux (k = 0.0097) was higher (P < 0.01) than that for DA efflux (k = 0.0033) and did not depend on the dose of L-DOPA. DOPAC/DA perifusate ratios were 2-fold those occurring in the tissues. 3. The levels of NA in renal tissues of rats given 30 and 100 mg/kg L-DOPS were, respectively, 3- and 6-fold those observed after the administration of 10 mg/kg L-DOPS. The administration of L-DOPS was also found to be accompanied by the accumulation in renal tissues of DOPEG; this was, however, not dose dependent. 4. The outflow of NA progressively declined with time and also reflected the tissue contents of NA; the outflow of DOPEG in the first collection period was found not to differ from those in subsequent collection periods. The rate constant for the loss of DOPEG (k = 0.0483) was 10-fold that for the loss of NA (k = 0.038). The DOPEG/NA ratio in the tissue was significantly lower than that in perifusate samples. In conclusion, the results presented here show that in cortical slices of the rat kidney a ranking order was obtained for the rate constants of efflux of k(DOPEG) much greater than k(DOPAC) > k(DA) = k(NA) suggesting that the outflow of DA, NA, DOPAC and DOPEG formed in tubular epithelial cells depends on their relative lipophilicity, as has been described in other cell types loaded with these catechol derivatives. These results also show that the amount of DA and NA which is leaving the compartment where the synthesis has occurred is a constant source for deamination into, respectively, DOPAC and DOPEG.