PROSTAGLANDIN EFFECTS ON THE CONTRACTILITY OF BOVINE TRABECULAR MESHWORK AND CILIARY MUSCLE

The ocular hypotensive activity of prostaglandins (PGs) has previously been demonstrated in various species including man. The underlying me chanism of action of prostanoids other than PGF(2 alpha) remains conte ntious. Because the trabecular meshwork and ciliary muscle are believe d to have a role in the regulation of aqueous humor outflow, the aim o f this study was to identify the PG-receptor subtypes present in these tissues using receptor-selective agonists. Contractions of isolated s trips of bovine trabecular meshwork and ciliary muscle were recorded i sometrically in continuously perfused tissue chambers. Contractile act ivity of PGs was determined relative to a maximally effective concentr ation of carbachol (1 mu M) as a standard agonist. The following prost anoids were employed: PGF(2 alpha), 17-phenyl PGF(2 alpha) (FP-recepto r agonists), sulprostone (EP(3) > EP(1)-agonist), AH13205 (EP(2)-agoni st), 11-deoxy PGE(1) (non-selective EP-agonist), and U-46619 (TP-agoni st). The thromboxane-mimetic U-46619 elicited a strong contraction of the trabecular meshwork with the highest concentration (1 mu M) being almost twice as efficacious (186.6%) as the maximal carbachol concentr ation, whereas the effect on the ciliary muscle was small. The U-46619 induced trabecular meshwork contraction could be blocked with a poten t and selective TP-receptor antagonist, 1 mu M SQ29548, indicating the involvement of TP-receptors. The other PC-analogs studied had either no or a small but statistically significant effect. Thus, 17-phenyl PG F(2 alpha) (1 mu M) weakly contracted the ciliary muscle (4.8%), sulpr ostone (1 mu M) the trabecular meshwork (10.1%). 11-deoxy PGE(1) (1 mu M) and AH13205 (10 mu M) elicited relaxations in both tissues precont racted with carbachol (1 mu M). The relaxant effects were more pronoun ced in trabecular meshwork (15.6% for 11-deoxy PGE, and 21.4% for AH13 205) than ciliary muscle (6.8 and 7.4% respectively). PGF(2 alpha) did not elicit a significant response in either tissue. Our studies sugge st the existence of TP- and EP(2)-receptors in the bovine trabecular m eshwork and potentially FP- and EP(2)-receptors in the ciliary muscle. In conclusion, thromboxane-mimetics and EP(2)-agonists have opposing activities on contractile elements in the meshwork and may modulate tr abecular outflow in a functionally antagonistic manner. Prostanoid eff ects on ciliary muscle appear rather modest compared to parasympathomi metic drugs. It is conceivable that TP-agonists may substantially affe ct trabecular outflow. (C) 1997 Academic Press Limited.