Characterization of brimonidine transport in retinal pigment epithelium

Invest Ophthalmol Vis Sci. 2006 Jan;47(1):287-94. doi: 10.1167/iovs.05-0189.


Purpose: To investigate the involvement of carrier-mediated transport mechanisms in brimonidine transport in retinal pigment epithelium (RPE).

Methods: The transport of [3H]-brimonidine in bovine RPE-choroid explants was evaluated in a modified Ussing chamber. The uptake of [3H]brimonidine was evaluated in differentiated ARPE-19 cells cultured on permeable transwell filters.

Results: The transport of brimonidine into (choroid-to-retina transport [inward]) and out of (retina-to-choroid transport [outward]) the eye in bovine RPE-choroid explants was temperature dependent. Both inward and outward brimonidine transport decreased at 5 microM compared with 10 nM. The melanin pigmentation of RPE did not significantly affect tissue permeability at either brimonidine dose. A saturable component was identified for the inward transport with the apparent Michaelis-Menten constant and a maximum transport rate of 51 microM and 148 pmol/(cm2 x h), respectively. Both apical (representing retina-to-choroid transport) and basolateral (representing choroid-to-retina transport) brimonidine uptake in ARPE-19 cells showed temperature dependence. Apical uptake was higher than basolateral uptake at 37 degrees C and was decreased to 70% in the presence of NaN3 or in the absence of extracellular Na+. Besides alpha2-agonists, apical uptake was inhibited by verapamil, desipramine, and quinidine, but not by MPP+ (1-methyl-4-phenylpyridinium), TEA (tetraethylammonium), decynium-22, carnitine, PHA (p-aminohippurate), alanine, or inosine. Basolateral brimonidine uptake increased by 35% at extracellular pH of 6 and decreased by 50% under cell-depolarized conditions of high medium K+ and 1 microM valinomycin. Temperature-dependent components of basolateral uptake were not saturated at doses up to 2 mM.

Conclusions: A carrier-mediated transport process for brimonidine in RPE was demonstrated in bovine RPE-choroid explants and polarized ARPE-19 cells. This transport system may play a significant role in modulating the movement of brimonidine into and out of the eye.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic Uptake Inhibitors / pharmacology
  • Adrenergic alpha-Agonists / metabolism*
  • Adrenergic alpha-Antagonists / pharmacology
  • Animals
  • Biological Transport, Active / drug effects
  • Biological Transport, Active / physiology
  • Blood-Retinal Barrier / physiology
  • Brimonidine Tartrate
  • Calcium Channel Blockers / pharmacology
  • Carrier Proteins / physiology*
  • Cattle
  • Cells, Cultured
  • Choroid / metabolism
  • Hydrogen-Ion Concentration
  • Melanins / metabolism
  • Pigment Epithelium of Eye / metabolism*
  • Quinoxalines / metabolism*
  • Retina / metabolism
  • Temperature
  • Time Factors


  • Adrenergic Uptake Inhibitors
  • Adrenergic alpha-Agonists
  • Adrenergic alpha-Antagonists
  • Calcium Channel Blockers
  • Carrier Proteins
  • Melanins
  • Quinoxalines
  • Brimonidine Tartrate