The effects of prostaglandin analogues on prostanoid EP1, EP2, and EP3 receptor-deficient mice.
OBJECTIVE
To determine the role of prostanoid EP receptors in the intraocular pressure (IOP)-lowering effect of prostaglandin analogues in EP receptor-deficient mice.


METHODS
Animals were bred and acclimatized in a 12-hour light-dark cycle. The diurnal IOP variation was measured by a microneedle method in EP1, EP2, and EP3 receptor-deficient mice (EP1KO, EP2KO and EP3KO) and in their wild-type (WT) background strain. IOP was measured in each mouse at night 3 hours after application of latanoprost, travoprost (0.004%), bimatoprost (0.03%), or unoprostone (0.12%). In WT and EP3KO mice, the effects of preapplication of diclofenac Na on drug-induced IOP reduction were examined.


RESULTS
Baseline IOPs were the same for all strains. Higher baseline IOPs were observed at night. Maximum IOP reduction occurred in WT mice 3 hours after latanoprost application during the day and night. Three hours after instillation at night, each of the four drugs lowered IOP significantly in WT, EP1KO, and EP2KO mice, whereas EP3KO a significantly lesser effect was induced by latanoprost, travoprost, and bimatoprost. Preapplication of diclofenac Na significantly attenuated drug-induced IOP reduction in WT but not in EP3KO mice.


CONCLUSIONS
Deficiency of EP receptors had no effect on physiological IOP. EP1 and EP2 receptors are not involved in prostaglandin analogue-induced IOP reduction, whereas EP3 receptors may play a role.
Ota
Takashi
T
Department of Ophthalmology, University of Tokyo School of Medicine, Japan.
Aihara
Makoto
M
Saeki
Tadashiro
T
Narumiya
Shuh
S
Araie
Makoto
M
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D002940:Circadian Rhythm / Q000187:drug effects; D004008:Diclofenac / Q000494:pharmacology; D007429:Intraocular Pressure / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009883:Ophthalmic Solutions / Q000494:pharmacology; D011461:Prostaglandins F, Synthetic / Q000494:pharmacology*; D018078:Receptors, Prostaglandin E / Q000172:deficiency / Q000502:physiology*; D058306:Receptors, Prostaglandin E, EP1 Subtype; D058307:Receptors, Prostaglandin E, EP2 Subtype; D058308:Receptors, Prostaglandin E, EP3 Subtype
D000959:Antihypertensive Agents; D009883:Ophthalmic Solutions; D011461:Prostaglandins F, Synthetic; C545636:Ptger1 protein, mouse; C545645:Ptger2 protein, mouse; C545648:Ptger3 protein, mouse; D018078:Receptors, Prostaglandin E; D058306:Receptors, Prostaglandin E, EP1 Subtype; D058307:Receptors, Prostaglandin E, EP2 Subtype; D058308:Receptors, Prostaglandin E, EP3 Subtype; D004008:Diclofenac