EFFECT OF ALPHA-HUMAN ATRIAL-NATRIURETIC-PEPTIDE ON THE SYNTHESIS OF DOPAMINE IN THE RAT-KIDNEY

1 The present study has examined the influence of alpha-human atrial n atriuretic peptide (alpha-hANP) on the synthesis of dopamine and its d eamination into 3,4-dihydroxyphenylacetic acid (DOPAC) in rat kidney s lices loaded with exogenous L-dihydroxyphenylalanine (L-DOPA). 2 Alpha -hANP (3.3 and 330 nM) was found to produce a marked reduction (63- 78 % reduction) in the time-dependent accumulation of newly-formed dopami ne and of its deaminated metabolite DOPAC in kidney slices loaded with 10-mu-M L-DOPA. Alpha-hANP (330 nM) was also found to decrease the ac cumulation of newly-formed dopamine (45- 66% reduction) and DOPAC (38- 61% reduction) in experiments in which increasing concentrations (1- 100-mu-M) of L-DOPA were used. This inhibitory effect was found to be potentiated by zaprinast (M&B 22,948; 10-mu-M), a guanosine cyclic 3', 5'-monophosphate (cyclic GMP) phosphodiesterase inhibitor. Alone, zapr inast also decreased the accumulation of both dopamine (54- 71% reduct ion) and DOPAC (73- 92% reduction). 3 In kidney homogenates, alpha-hAN P (330 nM) was found to affect neither the formation of dopamine nor i ts deamination to DOPAC. 4 Both alpha-hANP (330 nM) and zaprinast (10- mu-M) were found not to affect the formation of dopamine and DOPAC in kidney slices obtained from rats on a high salt diet during the previo us 6 weeks. A similar situation was also found to occur when kidney sl ices obtained from 24-months old rats were used. 5 The results obtaine d suggest that the inhibitory effect of alpha-hANP on the renal synthe sis of dopamine is dependent on the activation of a membrane-operated mechanism, coupled to the enzyme guanylate cyclase, controlling the en try of L-DOPA into the cells.