Localization of prostaglandin E receptor subtypes in the ciliary body of mouse eye

Prostaglandin E-2 (PGE(2)) markedly reduces intraocular pressure (IOP) when applied topically and induces strong relaxation of pre-contracted isolated ciliary muscle through PGE(2) receptor. Because the ciliary muscle relaxat ion reduces IOP by enhancing uveoscleral aqueous outflow, the ciliary muscl e where the existence of PGE(2) receptors has been demonstrated is thought to be one of the target tissues for PGE(2)-induced IOP reduction. To invest igate the subtypes of PGE(2) receptors in the ciliary muscle, the regional distribution of four PGE(2) receptor subtypes (EP1, EP2, EP3 and EP4) in th e mouse ciliary body was investigated by in situ hybridization using specif ic probes, Consistent messenger RNA signals for EP1 and EP4 receptors were expressed in the ciliary muscle, although signal levels for these subtypes were less potent as compared with the kidney, which was used as a reference organ. EP2 and EP3 signals were not detected. Stimulation of the EP4 recep tor activates adenylate cyclase, which should induce ciliary muscle relaxat ion. Therefore, the IOP reduction induced by PGE(2) analogs may be mediated by the EP4 receptor. In contrast, stimulation of the EP1 receptor is belie ved to promote intracellular Ca2+ mobilization, and hence should cause cili ary muscle contraction. Thus, the coexistence of EP1 and EP4 receptors in t he ciliary muscle suggests that the regulation of ciliary muscle tone by PG E(2) is based on a complex mechanism involving multiple receptor subtypes. (C) 2000 Academic Press.