Effect of nucleotide P2Y2 receptor agonists on outward active transport of fluorescein across normal blood-retina barrier in rabbit.
BACKGROUND
To evaluate the effect of nucleotide P2Y(2) receptor agonists INS542 and uridine 5'-triphosphate (UTP) on the outward active transport of fluorescein across rabbit blood-retina barrier (BRB) in vivo.


METHODS
Injection (0.1 ml) of INS542 (0.1 or 1mM), phosphate buffered solution, or UTP (1 or 10mM) was made in Dutch-belted rabbits. Differential vitreous fluorophotometry (DVF) was performed 3hr later and the fluorescein (F)/fluorescein monoglucuronide (FG) ratio was then calculated. F/FG ratios are inversely proportional to outward active transport of F across BRB at the level of the retinal pigment epithelium (RPE). In another set of experiments, the effect of 0.1 ml vitreous injection of INS542 (1mM) on F/FG ratios was evaluated at different time points ranging from 0.5 to 48hr before conducting DVF.


RESULTS
F/FG ratios obtained 3hr after intravitreal injection were as follows (mean+/-standard error): 0.49+/-0.14 (0.1mM INS542), 0.19+/-0.04 (1mM INS542), 0.48+/-0.09 (PBS), 0.40+/-0.08 (1mM UTP) and 0.36+/-0.05 (10mM UTP). The F/FG ratio for 1mM INS542 was significantly lower than in the other groups (P<0.05). In the time course experiments, a significant decrease in the F/FG ratios was observed between 1 and 12hr following administration of INS542 when compared with F/FG ratios obtained in the contralateral (untreated) eye.


CONCLUSIONS
Intravitreal administration of INS542 (but not UTP) enhances outward active transport of F across RPE in intact rabbit eye, indicating that activation of P2Y(2) receptors in vivo directly stimulates RPE active transport.
Takahashi
Junichi
J
Department of Ophthalmology, Asahikawa Medical College, 2-1 Midorigaoka-higashi, Asahikawa 078-8510, Japan. hikichi@asahikawa-med.ac.jp
Hikichi
Taiichi
T
Mori
Fumihiko
F
Kawahara
Atsushi
A
Yoshida
Akitoshi
A
Peterson
Ward M
WM
D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects / Q000502:physiology; D001813:Blood-Retinal Barrier / Q000187:drug effects* / Q000502:physiology; D019793:Fluorescein / Q000493:pharmacokinetics; D015590:Fluorophotometry / Q000379:methods; D008297:Male; D010857:Pigment Epithelium of Eye / Q000378:metabolism; D058910:Purinergic P2 Receptor Agonists; D011817:Rabbits; D018048:Receptors, Purinergic P2 / Q000502:physiology; D058473:Receptors, Purinergic P2Y2; D014544:Uridine Triphosphate / Q000494:pharmacology
D058910:Purinergic P2 Receptor Agonists; D018048:Receptors, Purinergic P2; D058473:Receptors, Purinergic P2Y2; D019793:Fluorescein; D014544:Uridine Triphosphate