L-3,4-dihydroxyphenylalanine and L-5-hydroxytryptophan share the same transporter in Opossum kidney cells

Int J Biochem Cell Biol. 1998 Feb;30(2):243-50. doi: 10.1016/s1357-2725(97)00115-5.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 5-Hydroxytryptophan / metabolism*
  • 5-Hydroxytryptophan / pharmacology
  • Amino Acid Transport Systems
  • Animals
  • Biological Transport
  • Carrier Proteins / metabolism*
  • Cells, Cultured
  • Dihydroxyphenylalanine / metabolism*
  • Dihydroxyphenylalanine / pharmacology
  • Kidney / drug effects
  • Kidney / metabolism*
  • Opossums
  • Stereoisomerism
  • Structure-Activity Relationship

Substances

  • Amino Acid Transport Systems
  • Carrier Proteins
  • Dihydroxyphenylalanine
  • 5-Hydroxytryptophan