L-3,4-dihydroxyphenylalanine and L-5-hydroxytryptophan share the same transporter in Opossum kidney cells.
Opossum kidney (OK) cells, which have the ability to synthesise dopamine and 5-HT, have been used as an in vitro model for the study of renal actions of dopamine and 5-hydroxytryptamine (5-HT). The present study reports on the uptake of their immediate precursors L-3,4-dihydroxyphenylalanine (L-DOPA) and L-5-hydroxytryptophan (L-5-HTP). IC50 values for L-5-HTP (1569 microM) obtained in the presence of a nearly saturating (250 microM) concentration of L-DOPA were 6-fold those obtained when using non-saturating (0.25 and 25 microM) concentrations of L-DOPA (251 and 266). Vmax values (in nmol mg protein-1 6 min-1) for L-DOPA uptake are identical in the absence (13.6) and the presence of 250 microM L-5-HTP (13.3), but K(m) values (microM) are significantly greater (P < 0.05) when L-DOPA uptake was studied in the presence of L-5-HTP (90 vs 1.79). IC50 values for L-DOPA (679 microM) obtained in the presence of a near saturating (250 microM) concentration of L-5-HTP were almost 3-fold those obtained when non-saturating (0.25 and 25 microM) concentrations of L-5-HTP were used (254 and 220). Vmax values (in nmol mg protein-1 6 min-1) for L-5-HTP uptake are identical in the absence (11.2) and the presence of 250 microM L-DOPA (11.7), but K(m) values (microM) are significantly greater (P < 0.05) when L-5-HTP uptake was studied in the presence of L-DOPA (103 vs 220). It is concluded that L-DOPA and L-5-HTP share the same transporter(s) and each compound exerts a competitive type of inhibition upon the other.
Gomes
P
P
Institute of Pharmacology and Therapeutics, Faculty of Medicine, Porto, Portugal.
Serrão
M P
MP
Vieira-Coelho
M A
MA
Soares-da-Silva
P
P
D006916:5-Hydroxytryptophan / Q000378:metabolism* / Q000494:pharmacology; D026905:Amino Acid Transport Systems; D000818:Animals; D001692:Biological Transport; D002352:Carrier Proteins / Q000378:metabolism*; D002478:Cells, Cultured; D004295:Dihydroxyphenylalanine / Q000378:metabolism* / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D009893:Opossums; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D026905:Amino Acid Transport Systems; D002352:Carrier Proteins; D004295:Dihydroxyphenylalanine; D006916:5-Hydroxytryptophan