title: Adenosine agonist regulation of outward active transport of fluorescein across retinal pigment epithelium in rabbits.
abstract: To investigate the effect of an adenosine agonist, 2-5'-N-ethylcarboxamidoadenosine (NECA), on the outward active transport of fluorescein across the retinal pigment epithelium (RPE) in rabbits. High (5x10(-4)-2x10(-3) M) and low (1x10(-5)-1x10(-4) M) concentrations of NECA or phosphate buffered saline (PBS) were intravitreously injected into Dutch-belted rabbits. Sodium fluorescein was injected intravenously 180 min after NECA. Differential vitreous fluorophotometry was performed 3 hr after the sodium fluorescein injection and the vitreal fluorescein/fluorescein monoglucuronide (F/FG) ratio then was calculated. The F/FG ratios are inversely proportional to the outward active transport of fluorescein across the RPE. Retinal detachments were induced by injection of PBS into the subretinal space after the intravitreous injection of low- or high-dose NECA or PBS, and the size of the blebs was monitored. In eyes that received a low-dose injection of NECA, the F/FG ratio was higher compared with controls (P<0.05); in eyes that received a high-dose intravitreal injection, the F/FG ratio was significantly lower compared with controls (P<0.05). The effect of low-dose NECA on the F/FG ratio was suppressed by the A2 receptor antagonist, ZM241385, and the effect of high-dose NECA was suppressed by the A1 receptor antagonist, 8-cyclopentyl-1, 3-dipropylxanthine. The A3 receptor antagonist MRS1191 did not influence the effect of low- or high-dose NECA. Intravitreal injection of high-dose NECA enhanced the reabsorption of subretinal fluid compared with PBS; however, low-dose NECA inhibited reabsorption of subretinal fluid (P<0.02 and 0.05, respectively). Intravitreous injection of high-dose NECA accelerates the active outward transport across the RPE via A1 receptors and low-dose NECA decelerates it via A2 receptors.
authors.affiliation: Department of Ophthalmology, Asahikawa Medical College, 2-1 Midorigaoka-Higashi, Asahikawa 078-8510, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kawahara
authors.forename: Taiichi
authors.initials: T
authors.lastname: Hikichi
authors.forename: Norihiko
authors.initials: N
authors.lastname: Kitaya
authors.forename: Junichi
authors.initials: J
authors.lastname: Takahashi
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Mori
authors.forename: Akitoshi
authors.initials: A
authors.lastname: Yoshida
mesh_terms: D000241:Adenosine / Q000378:metabolism; D058916:Adenosine A1 Receptor Antagonists; D058917:Adenosine A2 Receptor Antagonists; D058918:Adenosine A3 Receptor Antagonists; D019830:Adenosine-5'-(N-ethylcarboxamide) / Q000494:pharmacology*; D000818:Animals; D001693:Biological Transport, Active; D004095:Dihydropyridines / Q000008:administration & dosage; D019793:Fluorescein / Q000008:administration & dosage / Q000032:analysis / Q000493:pharmacokinetics*; D005452:Fluoresceins / Q000032:analysis; D015590:Fluorophotometry / Q000379:methods; D007275:Injections, Intravenous; D008297:Male; D010857:Pigment Epithelium of Eye / Q000378:metabolism*; D058915:Purinergic P1 Receptor Antagonists; D011817:Rabbits; D012163:Retinal Detachment / Q000378:metabolism; D014227:Triazines / Q000008:administration & dosage; D014230:Triazoles / Q000008:administration & dosage; D014970:Xanthines / Q000494:pharmacology
chemical_list: D058916:Adenosine A1 Receptor Antagonists; D058917:Adenosine A2 Receptor Antagonists; D058918:Adenosine A3 Receptor Antagonists; D004095:Dihydropyridines; D005452:Fluoresceins; C107728:MRS 1191; D058915:Purinergic P1 Receptor Antagonists; D014227:Triazines; D014230:Triazoles; D014970:Xanthines; C097270:ZM 241385; D019830:Adenosine-5'-(N-ethylcarboxamide); C041357:fluorescein glucuronide; C051360:1,3-dipropyl-8-cyclopentylxanthine; D000241:Adenosine; D019793:Fluorescein