title: Prostaglandin effects on the contractility of bovine trabecular meshwork and ciliary muscle.
abstract: The ocular hypotensive activity of prostaglandins (PGs) has previously been demonstrated in various species including man. The underlying mechanism of action of prostanoids other than PGF2 alpha remains contentious. Because the trabecular meshwork and ciliary muscle are believed to have a role in the regulation of aqueous humor outflow, the aim of this study was to identify the PG-receptor subtypes present in these tissues using receptor-selective agonists. Contractions of isolated strips of bovine trabecular meshwork and ciliary muscle were recorded isometrically in continuously perfused tissue chambers. Contractile activity of PGs was determined relative to a maximally effective concentration of carbachol (1 microM) as a standard agonist. The following prostanoids were employed: PGF2 alpha, 17-phenyl PGF2 alpha (FP-receptor agonists), sulprostone (EP3 > EP1-agonist), AH13205 (EP2-agonist), 11-deoxy PGE1 (non-selective EP-agonist), and U-46619 (TP-agonist). The thromboxane-mimetic U-46619 elicited a strong contraction of the trabecular meshwork with the highest concentration (1 microM) being almost twice as efficacious (186.6%) as the maximal carbachol concentration, whereas the effect on the ciliary muscle was small. The U-46619 induced trabecular meshwork contraction could be blocked with a potent and selective TP-receptor antagonist, 1 microM SQ29548, indicating the involvement of TP-receptors. The other PG-analogs studied had either no or a small but statistically significant effect. Thus, 17-phenyl PGF2 alpha (1 microM) weakly contracted the ciliary muscle (4.8%), sulprostone (1 microM) the trabecular meshwork (10.1%), 11-deoxy PGE1 (1 microM) and AH13205 (10 microM) elicited relaxations in both tissue precontracted with carbachol (1 microM). The relaxant effects were more pronounced in trabecular meshwork (15.6% for 11-deoxy PG1 and 21.4% for AH13205) than ciliary muscle (6.8 and 7.4% respectively). PGF2 alpha did not elicit a significant response in either tissue. Our studies suggest the existence of TP- and EP2-receptors in the bovine trabecular meshwork and potentially FP- and EP2-receptors in the ciliary muscle. In conclusion, thromboxane-mimetics and EP2-agonists have opposing activities on contractile elements in the meshwork and may modulate trabecular outflow in a functionally antagonistic manner. Prostanoid effects on ciliary muscle appear rather modest compared to parasympathomimetic drugs. It is conceivable that TP-agonists may substantially affect trabecular outflow.
authors.affiliation: Allergan, Inc., Irvine, CA 92612, USA.
authors.forename: A H
authors.initials: AH
authors.lastname: Krauss
authors.forename: M
authors.initials: M
authors.lastname: Wiederholt
authors.forename: A
authors.initials: A
authors.lastname: Sturm
authors.forename: D F
authors.initials: DF
authors.lastname: Woodward
mesh_terms: D000818:Animals; D002417:Cattle; D002924:Ciliary Body / Q000187:drug effects* / Q000502:physiology; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D011465:Prostaglandins, Synthetic / Q000494:pharmacology*; D011982:Receptors, Prostaglandin / Q000819:agonists* / Q000037:antagonists & inhibitors*; D018078:Receptors, Prostaglandin E / Q000819:agonists; D014129:Trabecular Meshwork / Q000187:drug effects* / Q000502:physiology
chemical_list: D011465:Prostaglandins, Synthetic; D011982:Receptors, Prostaglandin; D018078:Receptors, Prostaglandin E