title: Aqueous flare elevation induced by transcorneal application of highly selective agonists for prostaglandin E2 receptor subtypes in pigmented rabbits: effect of tetramethylpyrazine.
abstract: We examined the disruptive effect of highly selective agonists for prostaglandin E2 receptor subtypes (EP1, EP2, EP3 and EP4) on the blood-aqueous barrier, and evaluated the inhibitory effect of tetramethylpyrazine, an active component of Ligusticum wallichii, on the elevation of aqueous flare induced by the EP agonists in pigmented rabbits. Highly selective EP agonists (ONO-DI-004, EP1 agonist; ONO-AE1-259-01, EP2 agonist; ONO-AE-248, EP3 agonist; ONO-AE1-329, EP4 agonist) at 12.5 to 250 microg/ml were transcorneally administered to the eyes of pigmented rabbits using a glass cylinder. Animals were pretreated intravenously with tetramethylpyrazine (10 or 30 mg/kg) 30 minutes before application of the EP2 or the EP4 agonist. Aqueous flare was measured using a laser flare-cell meter. Aqueous flare intensity was expressed as the area under the curve (AUC) in arbitrary units. After administration of ONO-AE1-259-01 or ONO-AE1-329, aqueous flare increased and then gradually decreased. ONO-DI-004 and ONO-AE-248 had almost no effect on aqueous flare elevation. The AUC of eyes in rabbits pretreated with tetramethylpyrazine, 10 or 30 mg/kg i.v., was significantly smaller than that of eyes in rabbits treated with ONO-AEI-259-01 alone. The AUC of eyes in rabbits pretreated with tetramethylpyrazine, 10 or 30 mg/kg i.v., was not significantly smaller than that of eyes in rabbits treated with ONO-AEI-329 only. The results indicated that EP2 and EP4 agonists induced aqueous flare elevation in pigmented rabbits, and that tetramethylpyrazine inhibited the aqueous flare elevation induced by the EP2 agonist but did not suppress the elevation induced by the EP4 agonist.
authors.affiliation: Department of Ophthalmology, Toyama Medical and Pharmaceutical University, Sugitani, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Kitagawa
authors.forename: S
authors.initials: S
authors.lastname: Hayasaka
authors.forename: K
authors.initials: K
authors.lastname: Watanabe
authors.forename: Y
authors.initials: Y
authors.lastname: Nagaki
mesh_terms: D000818:Animals; D001082:Aqueous Humor / Q000187:drug effects* / Q000378:metabolism; D019540:Area Under Curve; D018916:Blood-Aqueous Barrier / Q000187:drug effects / Q000502:physiology*; D003315:Cornea / Q000378:metabolism*; D004058:Diffusion; D015232:Dinoprostone / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000493:pharmacokinetics / Q000494:pharmacology*; D004347:Drug Interactions; D008297:Male; D015394:Molecular Structure; D010858:Pigmentation; D020033:Protein Isoforms / Q000378:metabolism; D011719:Pyrazines / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D011817:Rabbits; D018078:Receptors, Prostaglandin E / Q000819:agonists* / Q000378:metabolism; D013997:Time Factors; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: C121546:ONO AE 248; D020033:Protein Isoforms; D011719:Pyrazines; D018078:Receptors, Prostaglandin E; D014665:Vasodilator Agents; D015232:Dinoprostone; C017953:tetramethylpyrazine