Reciprocal renal effects of dopamine and 5-hydroxytryptamine formed within the rat kidney.
1. Clearance of inulin and p-aminohippurate and excretion of water and sodium were measured for eight to 11 clearance periods of 20 min duration in anaesthetized, 3% volume-expanded rats, before and after intravenous infusions of the amino acids L-dopa (L-3,4-dihydroxyphenylalanine) and 5-hydroxytryptophan. During the final two clearance periods, the peripheral decarboxylase inhibitor, carbidopa (S-alpha-hydrazino-3,4-dihydroxy-alpha-methylbenzenepropanoic acid monohydrate), was infused additionally. 2. Renal formation of dopamine (3,4-dihydroxyphenethylamine) and 5-hydroxytryptamine was demonstrated during infusions of L-dopa and 5-hydroxytryptophan, respectively; carbidopa blocked the renal formation of these biogenic amines. 3. During infusion of dopa, a diuresis and a natriuresis were observed; during the infusion of 5-hydroxytryptophan, slight reductions in clearances of inulin and p-aminohippurate, but significant reductions in sodium and water excretion, were measured. 4. The addition of carbidopa diminished diuretic and natriuretic responses to dopa as renal dopamine excretion decreased; the infusion of carbidopa also ameliorated the antinatriuretic and antidiuretic effects of 5-hydroxytryptophan, as 5-hydroxytryptamine excretion decreased. 5. Although dopa and 5-hydroxytryptophan are substrates for the same enzyme, aromatic L-amino-acid decarboxylase, simultaneous infusions of both amino acids at comparable rates gave no evidence of competitive inhibition of amine synthesis. However, the infusion of dopa, after 5-hydroxytryptophan, decreased its antinatriuretic and antidiuretic effects. 6. These data raise the possibility that dopamine and 5-hydroxytryptamine are formed as reciprocal intrarenal hormones by the identical enzyme, aromatic L-amino-acid decarboxylase, which is located within cells of the renal tubule.
Itskovitz
H D
HD
Department of Medicine, New York Medical College, Valhalla 10595.
Chen
Y H
YH
Stier
C T
CT
D006916:5-Hydroxytryptophan / Q000494:pharmacology; D000818:Animals; D004295:Dihydroxyphenylalanine / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D007262:Infusions, Intravenous; D007444:Inulin / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008657:Metabolic Clearance Rate; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000378:metabolism*; D010130:p-Aminohippuric Acid / Q000378:metabolism
D012701:Serotonin; D004295:Dihydroxyphenylalanine; D007444:Inulin; D006916:5-Hydroxytryptophan; D004298:Dopamine; D010130:p-Aminohippuric Acid