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 natriuretic peptide (alpha-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). 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 dopamine and of its deaminated metabolite DOPAC in kidney slices loaded with 10 microM L-DOPA. alpha-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 microM) of L-DOPA were used. This inhibitory effect was found to be potentiated by zaprinast (M&B 22,948; 10 microM), 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). 3. In kidney homogenates, alpha-hANP (330 nM) was found to affect neither the formation of dopamine nor its deamination to DOPAC. 4. Both alpha-hANP (330 nM) and zaprinast (10 microM) 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.5. The results obtained suggest that the inhibitory effect of alpha-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.
Soares-da-Silva
P
P
Department of Pharmacology and Therapeutics, Faculty of Medicine, Porto, Portugal.
Fernandes
M H
MH
D015106:3',5'-Cyclic-GMP Phosphodiesterases / Q000037:antagonists & inhibitors; D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000375:Aging / Q000378:metabolism; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D004298:Dopamine / Q000096:biosynthesis*; D066298:In Vitro Techniques; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D007980:Levodopa / Q000378:metabolism; D008297:Male; D011688:Purinones / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012982:Sodium, Dietary / Q000008:administration & dosage
D011688:Purinones; D012982:Sodium, Dietary; D015102:3,4-Dihydroxyphenylacetic Acid; D007980:Levodopa; D009320:Atrial Natriuretic Factor; D015106:3',5'-Cyclic-GMP Phosphodiesterases; C011145:zaprinast; D004298:Dopamine