Characterization of brimonidine transport in retinal pigment epithelium.

نویسندگان

  • Ning Zhang
  • Ram Kannan
  • Curtis T Okamoto
  • Stephen J Ryan
  • Vincent H L Lee
  • David R Hinton
چکیده

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.

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عنوان ژورنال:
  • Investigative ophthalmology & visual science

دوره 47 1  شماره 

صفحات  -

تاریخ انتشار 2006