Renal dopamine synthesis from precursors.
In the Wistar rat in vivo L-dopa (10 mg/kg, subcutaneously) was shown to have the characteristics of a kidney-directed dopamine (DA) prodrug: two daily injections increased 24 h urinary DA excretion 450-fold but had no systemic effects on blood pressure and heart rate. In inactin-anesthesized rats, L-dopa increased natriuresis, diuresis and renal blood flow; these effects were linked to endorenal DA synthesis and to DA-1 receptor stimulation since they were suppressed by both carbidopa and SCH 23390. In the isolated perfused rat kidney, DA was synthesized from L-dopa with a greater yield than from gludopa. In nonfiltering kidneys, L-dopa metabolism was not limited when the access to dopa decarboxylase was restricted to the basolateral membrane. The same was not true for gludopa, for which the basolateral metabolism was low.
Barthelmebs
M
M
Institut de Pharmacologie, URA D0589 CNRS, Faculté de Médecine, Université Louis Pasteur, Strasbourg, France.
Vailly
B
B
Velly
J
J
Ehrhardt
J D
JD
Grima
M
M
Imbs
J L
JL
D000818:Animals; D004295:Dihydroxyphenylalanine / Q000031:analogs & derivatives / Q000378:metabolism; D004298:Dopamine / Q000096:biosynthesis*; D066298:In Vitro Techniques; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D007980:Levodopa / Q000378:metabolism / Q000494:pharmacology; D008297:Male; D010477:Perfusion; D011355:Prodrugs / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D011355:Prodrugs; D007980:Levodopa; C017342:gamma-glutamyl DOPA; D004295:Dihydroxyphenylalanine; D004298:Dopamine