Effect of α‐human atrial natriuretic peptide on the synthesis of dopamine in the rat kidney

Abstract

The present study has examined the influence of α‐human atrial natriuretic peptide (α‐hANP) on the synthesis of dopamine and its deamination into 3,4‐dihydroxyphenylacetic acid (DOPAC) in rat kidney slices loaded with exogenous l‐dihydroxyphenylalanine (l‐DOPA). α‐hANP (3.3 and 330 nm) was found to produce a marked reduction (63– 78% reduction) in the time‐dependent accumulation of newly‐formed dopamine and of its deaminated metabolite DOPAC in kidney slices loaded with 10 μm l‐DOPA. α‐hANP (330 nm) was also found to decrease the accumulation of newly‐formed dopamine (45– 66% reduction) and DOPAC (38– 61% reduction) in experiments in which increasing concentrations (1– 100 μm) of l‐DOPA were used. This inhibitory effect was found to be potentiated by zaprinast (M&B 22,948; 10 μm), a guanosine cyclic 3′,5′‐monophosphate (cyclic GMP) phosphodiesterase inhibitor. Alone, zaprinast also decreased the accumulation of both dopamine (54–71% reduction) and DOPAC (73– 92% reduction). In kidney homogenates, α‐hANP (330 nm) was found to affect neither the formation of dopamine nor its deamination to DOPAC. Both α‐hANP (330 nm) and zaprinast (10 μm) were found not to affect the formation of dopamine and DOPAC in kidney slices obtained from rats on a high salt diet during the previous 6 weeks. A similar situation was also found to occur when kidney slices obtained from 24‐months old rats were used. The results obtained suggest that the inhibitory effect of α‐hANP on the renal synthesis of dopamine is dependent on the activation of a membrane‐operated mechanism, coupled to the enzyme guanylate cyclase, controlling the entry of l‐DOPA into the cells. 1992 British Pharmacological Society