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The renal handling of dopamine originating from L-dopa and gamma-glutamyl-L-dopa.
Authors:M. Pestana and P. Soares-da-Silva
Affiliation:Department of Pharmacology and Therapeutics, Faculty of Medicine, Porto, Portugal.
Abstract:1. The formation and outflow of dopamine and its deaminated metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) was studied in cortical fragments of the rat kidney loaded with L-beta-3,4-dihydroxyphenylalanine (L-dopa) or gamma-glutamyl-L-dopa (GluDOPA). Dopamine and DOPAC in the tissues and in the effluent were assayed by means of h.p.l.c. with electrochemical detection. 2. In rats given 30 mg kg-1 L-dopa, tissue and outflow levels of both dopamine and DOPAC were 3 fold those observed with a lower dose of L-dopa (10 mg kg-1). In rats given GluDOPA (16.7 mg kg-1) levels of dopamine in renal tissues and in perifusate samples were found to be higher than those obtained with an equimolar dose of L-dopa (10 mg kg-1); however, no significant difference was observed for DOPAC. The outflow of both dopamine and DOPAC in kidney slices of rats injected with L-dopa (10 and 30 mg kg-1) or GluDOPA (16.7 mg kg-1) was found to decline monophasically with similar slopes of decline. The rate constants of loss (k, min-1) of DOPAC (10 mg kg-1 L-DOPA, k = 0.0070; 30 mg kg-1 L-DOPA, k = 0.0087; 16.7 mg kg-1 GluDOPA, k = 0.0080) were 2 to 3 fold those of dopamine (10 mg kg-1 L-dopa, k = 0.0027; 30 mg kg-1 L-DOPA, k = 0.0034; 16.7 mg kg-1 GluDOPA, k = 0.0030). With both precursors the DOPAC/dopamine ratio in perifusate samples were 2.0 fold those in the tissues.(ABSTRACT TRUNCATED AT 250 WORDS)
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