EFFECT OF TYPE-A AND B MONOAMINE-OXIDASE SELECTIVE-INHIBITION BY RO-41-1049 AND RO-19-6327 ON DOPAMINE OUTFLOW IN RAT-KIDNEY SLICES

1 The influence of pargyline and of selective inhibitors of type A and B monoamine oxidase (MAO), Po 41-1049 and Po 19-6327 respectively, on the outflow of dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC) in slices of rat renal cortex loaded with exogenous L-3,4-dihydroxypheny lalanine (L-DOPA) was examined. Dopamine and DOPAC in the tissues and in the effluent were assayed by means of h.p.l.c. with electrochemical detection. 2 The levels of newly-formed dopamine and DOPAC in the per ifusate decreased progressively with time. In control conditions, DOPA C/dopamine ratios in the perifusate were 3 to 5 fold those in the tiss ue and were found to increase progressively with time. The addition of pargyline (100 mu M), produced a marked decrease in the outflow level s of DOPAC (45 to 54% reduction) and significantly increased the level s of dopamine in the effluent (102 to 158% increase); DOPAC/dopamine r atios in the perifusate remained stable throughout the perifusion and were similar to those found in the tissues. The addition of the MAO-A inhibitor Po 41-1049 to the perifusion fluid also significantly decrea sed DOPAC outflow (41% to 54% reduction) and increased dopamine outflo w (19% to 80% increase). In the presence of Po 41-1049 DOPAC/dopamine ratios in the perifusate were lower (P<0.01) than in controls; in cont rast with the effect of pargyline, this ratio was found to increase (P <0.01) throughout the perifusion period. Po 19-6327 did not reduce the outflow of DOPAC, but significantly increased (by 40-60%) that of dop amine. In the presence of Po 19-6237, the proportion of DOPAC to dopam ine in the perifusate was similar to that of controls and significantl y increased throughout the perifusion; however, this increase was less than that observed in the control group. 3 When benserazide (50 mu M) was added to the perifusion fluid, the levels of both dopamine and DO PAC in the effluent were similar to those observed in the absence of b enserazide. However, in the presence of benserazide, DOPAC/dopamine ra tios in the perifusate did not increase with time. In conditions of de carboxylase inhibition, the effects of pargyline, Ro 41-1049 and Ro 19 -6327 on dopamine and DOPAC outflow were less pronounced than in exper iments conducted in the absence of benserazide. 4 In conclusion, the r esults presented here show that the fraction of newly-formed dopamine which leaves the compartment where the synthesis has occurred is a con stant;source for deamination into DOPAC. The results provide evidence favouring the view that MAO-A is the main form of the enzyme involved in this process; however, the data described here suggest that dopamin e would also have access to MAO-B.