November 1999
Volume 40, Issue 12
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Physiology and Pharmacology  |   November 1999
Responses of Intraocular Pressure and the Pupil of Feline Eyes to Prostaglandin EP1 and FP Receptor Agonists
Author Affiliations
  • Parimal Bhattacherjee
    From the Department of Ophthalmology and Visual Sciences, University of Louisville, Kentucky.
  • Billy Shawn Williams
    From the Department of Ophthalmology and Visual Sciences, University of Louisville, Kentucky.
  • Christopher A. Paterson
    From the Department of Ophthalmology and Visual Sciences, University of Louisville, Kentucky.
Investigative Ophthalmology & Visual Science November 1999, Vol.40, 3047-3053. doi:
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      Parimal Bhattacherjee, Billy Shawn Williams, Christopher A. Paterson; Responses of Intraocular Pressure and the Pupil of Feline Eyes to Prostaglandin EP1 and FP Receptor Agonists. Invest. Ophthalmol. Vis. Sci. 1999;40(12):3047-3053.

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Abstract

purpose. Previous studies suggested that FP receptors do not mediate the relaxation of the ciliary muscle and reduction of intraocular pressure in cats by prostaglandin (PG) F. The present study was undertaken to determine whether the reduction of intraocular pressure in cats induced by PGF is mediated by FP or other prostaglandin receptors.

methods. One eye of each cat was treated topically with prostaglandin F, fluprostenol (FP receptor agonist), or 17-phenyl trinor PGE2 (EP1 receptor agonist) in a dose range of 12.5 to 50 μg. The effects of SC19220 and SC51089 (EP1 receptor antagonists), BWA868c, and SQ29548 (DP and TP receptor antagonists, respectively) on the intraocular response to PGF were also examined. At intervals up to 6 hours after treatment, intraocular pressure was measured with a pneumotonometer, and pupil diameters were measured with a millimeter ruler.

results. In the dose ranges used, PGF and 17-phenyl trinor PGE2 decreased intraocular pressure and pupil diameter. The greatest reduction of intraocular pressure by 50.0 μg PGF was 5.0 ± 1.4 mm Hg, whereas that by 50 μg 17-phenyl trinor PGE2 was 6.2 ± 1.5 mm Hg. The isopropyl ester of PGF at a dose of 1.25 μg reduced intraocular pressure by 3.75 ± 0.25 mm Hg at 2 hours. At doses up to100 μg, fluprostenol did not decrease intraocular pressure but did reduce pupil diameter. SC19220, a weak but selective EP1 receptor antagonist, inhibited the intraocular pressure response to both PGF and 17-phenyl trinor PGE2. The more potent EP1 receptor antagonist SC51089 had a greater inhibitory effect than SC19220 on the intraocular pressure response to PGF. Both of these antagonists had a small but non–dose dependent and statistically insignificant effect on the pupil response to PGF. These observations suggest that in cats, intraocular pressure and pupil responses to PGF are mediated by EP1 and FP receptors, respectively. However, SC19220 significantly and dose-dependently inhibited the pupil response to 17-phenyl trinor PGE2, suggesting that EP1 receptors mediate pupil response to this agonist. DP and TP receptor antagonists at doses 5- to 20-fold greater than the IC50 values had no effect on the ocular hypotensive response to PGF. The concurrent administration of 12.5μ g of each of PGF and 17-phenyl trinor PGE2 did not produce an additive effect on intraocular pressure, indicating that in cats PGF and 17-phenyl trinor PGE2 act on the same receptor type.

conclusions. These results suggest that a significant proportion of the ocular hypotensive action of PGF in cats is mediated by EP1 but not by FP receptor. Evidence was also provided to show that 17-phenyl trinor PGE2 is an ocular hypotensive agent in cats.

Prostaglandins (PGs), administered topically in appropriate concentrations, reduce intraocular pressure (IOP) in rabbits, cats, and humans. 1 2 3 4 Prostaglandin F in particular is an extremely potent ocular hypotensive agent and is currently thought to reduce intraocular pressure by increasing uveoscleral outflow, 5 6 perhaps through the mediation of discrete FP receptors in the ciliary muscle. 7 8 9 10 However, one report suggests that the ocular hypotensive action of PGF in the cat is not mediated by FP receptors. 11 Also, PGF has been reported to have a weak relaxant effect on cat ciliary muscle, whereas the more selective FP receptor agonist 17-phenyl trinor PGF was without effect. 12 13 These observations suggest that increased uveoscleral outflow in response to PGF may not be mediated by FP receptors. Recently, a study on the generation of second messengers reported that 17-phenyl trinor PGE2, but not PGF, stimulated the formation of inositol phosphates in cat ciliary muscles. 14 To examine whether the ocular hypotensive action of PGF is mediated by EP1 or other PG receptors, we investigated the response of IOP and pupil diameter in cats to PGF and fluprostenol, FP receptor agonists, and an EP1 receptor agonist, 17-phenyl trinor PGE2
Methods
Materials
All natural and synthetic prostaglandins and SQ29548 were purchased from Cayman Chemical (Ann Arbor, MI). The EP1 receptor antagonists SC19220 and SC51089 were a gift from Searle Research and Development (Skokie, IL). DP receptor antagonist BWA868c was supplied by Glaxo–Wellcome (Hertfordshire, UK). Alcaine (0.5% proparacaine) was purchased from Alcon Laboratories (Ft. Worth, TX). 
Measurement of IOP and Pupil Diameter
All animals used were treated in accordance with the ARVO Statement for the Use of Animals in Ophthalmic and Vision Research. Twenty cats (2–3 kg) were domesticated for 4 months and trained to accept topical administration of saline or local anesthetic drops and the application of a pneumotonometer tip to the cornea to measure IOP. These cats were randomly divided into groups of three to six cats depending on the experimental design of each experiment. A washout period of 15 to 30 days was allowed between separate experiments. Before the experiments with prostaglandins, IOPs of the eyes treated with the vehicle and untreated contralateral eyes of all the cats were measured for a 6-hour period using a pneumotonometer (model 30-Classic; Mentor O & O, Norwell, MA). This pneumotonometer was calibrated for human eyes by the manufacturer and has been used to measure IOP of cats 15 16 17 without further calibration. We did not calibrate it for cat eyes because our study is not concerned with the physiology or comparative physiology of IOP. In our pharmacological study, we were interested in the effects of prostaglandins on IOP and the differences between the treated and the control eyes. Intraocular pressure measured in cats using this pneumotonometer in the present study was in the range of 17 to 19 mm Hg compared with 14 to 20, 15 17 to 20, 16 and 19 to 20 mm Hg 17 as reported previously. 
Prostaglandins, diluted in dimethyl sulfoxide (DMSO), were instilled onto the cornea of one eye in a 25-μl volume; the contralateral eye received the same volume of DMSO alone. In experiments with antagonists, eyes were pretreated 30 minutes before PGF with an appropriate antagonist. This time of pretreatment with the antagonists was determined in our preliminary studies with SC19220, in which it was observed that 10 to 30 minutes’ pretreatment was satisfactory to exert its inhibitory effect. Intraocular pressure was measured at 1 and 2 hours before and at 0, 1, 2, 4, and 6 hours after treatment with prostaglandin receptor agonists and at the same time of the day beginning at 9:00 AM. Before the measurement of IOP, a drop of local anesthetic, proparacaine hydrochloride (0.5%), was instilled onto the cornea. Horizontal pupil diameter before and after treatment was measured with a millimeter ruler. 
Expression and Analysis of Data
Both the IOP and pupil diameter data were expressed as the difference between drug-treated eyes and DMSO-treated contralateral eyes. The significance of the difference between the mean values of DMSO- and drug-treated eyes at any given time was evaluated by an ANOVA test using Microsoft Excel 5.0. The IC50 values were calculated using GraphPad Prizm (version 2.01; GraphPad Software, San Diego, CA) and Lotus 123-R4.01. 
Results
The effects of PGF, fluprostenol, and 17-phenyl trinor PGE2 on IOP and the pupil diameters of cats are summarized in Figures 1 and 3 . In the dose range of 12.5 to 50.0 μg, PGF reduced IOP without an initial phase of ocular hypertension. All doses of PGF lowered IOP, beginning 1 hour after the treatment. The greatest reduction, 5.0 ± 0.4 mm Hg, occurred between 1 and 2 hours after treatment with 50.0 μg of PGF (Fig. 1A) . The IOP returned to baseline value within 6 hours after treatment with all doses of PGF. In contrast, the response of IOP to 1.25 μg isopropyl ester of PGF was significantly greater than that to PGF (Fig. 1A) . This was not unexpected because the ester forms of prostaglandins achieve greater intraocular concentrations than do their acidic forms. 18 17-Phenyl trinor PGE2 also reduced intraocular pressure in a dose-dependent manner, with an onset and duration of action similar to those of PGF (Fig. 1B) . The greatest reduction of IOP by 50.0 μg of 17-phenyl trinor PGE2 was 6.2 ± 1.5 mm Hg at 2 hours after treatment. Fluprostenol, in doses up to 100 μg, did not reduce IOP (Fig. 1C) . Intraocular pressures of the eyes treated with vehicle or 100 μg SC19220 and the contralateral eyes of the 50 μg PGF–treated group are shown in Figure 2 . It is obvious that feline IOP remains stable during a 6-hour experimental period with minor variations. At the maximal concentration, none of the agonists induced a contralateral effect. Furthermore, SC19220 alone at 100 μg had no effect on IOP. 
Prostaglandin F, its isopropyl ester 17-phenyl trinor PGE2, and fluprostenol all dose-dependently induced miosis. The time course and duration of the pupil response to these agonists were similar to those of the IOP responses (Figs. 3 A, 3B, and 3C). As shown in Table 1 , the selective EP1 receptor antagonist SC19220 inhibited the IOP response to PGF or 17-phenyl trinor PGE2 as well as isopropyl PGF. The highest concentration of SC19220 blocked the IOP response to PGF by 38%, compared with the 80% and 94% reductions of the responses to17-phenyl trinor PGE2 and isopropyl PGF, respectively. SC51089, a more potent EP1 receptor antagonist than SC19220, confirmed the above observation on PGF response. The results (Table 1) show that SC51089 is more effective than SC19220 in inhibiting the IOP response to PGF. Inhibition of the pupil response to PGF by SC19220 or SC51089 was not dose-dependent or statistically insignificant; whereas the inhibition of 17-phenyl trinor PGE2 response by SC19220 was dose-dependent and significant (SC51089 was not tested against 17-phenyl trinor PGE2). The highly potent DP receptor antagonist BWA868c (IC50, 1 nM) at 0.3 ng (25 nM) or 1.2ng (100nM) and TP receptor antagonist SQ29548 (IC50, 10 nM) at 0.48 ng (50 nM) or 0.96 ng (100 nM) did not affect the ocular hypotensive response to PGF (Table 1) . We performed one classic pharmacological experiment to determine whether PGF and 17-phenyl trinor PGE2 are acting on the same or different receptor type. Figure 4 shows that 12.5 μg of each of these agonists administered together did not produce a greater hypotensive effect than when administered alone. This observation suggests that these two agonists activated the same EP1 receptors. If they had been acting on different receptor types, the IOP response would have been additive. 
Discussion
In the present studies, we demonstrated for the first time that a single dose of 17-phenyl trinor PGE2, an EP1 receptor agonist, reduced IOP and pupil diameter in cats. Prostaglandin F also reduced IOP and pupil diameter in a dose-dependent manner. At a low dose of 1.25 μg, the isopropyl ester of PGF also reduced IOP. To maintain consistency, we primarily used prostaglandins instead of their isopropyl esters because two of the agonists used, fluprostenol and 17-phenyl trinor PGE2, are not available as isopropyl esters. 
Intraocular pressure responses to PGF and its isopropyl ester are consistent with previous reports that these compounds are potent ocular hypotensive and miotic agents in cats. 2 18 19 Fluprostenol, a more selective FP receptor agonist than PGF, did not lower IOP but was as potent as PGF and 17-phenyl trinor PGE2 as a miotic agent. The EP1 receptor antagonist SC19220 at a 100-μg dose significantly inhibited the reduction in IOP by PGF, its isopropyl ester, and 17-phenyl trinor PGE2. The doses of the antagonist used in the present study appear to be high. However, it should be emphasized that, although this EP1 antagonist is highly selective, it is not potent, particularly in vivo. Therefore, it is not surprising that high doses were needed to exert an inhibitory effect. The more potent EP1 receptor antagonist SC51089, at a dose of only 10 μg, inhibited 80% of the IOP response to PGF, suggesting that the ocular hypotensive action of PGF2x is mediated by EP1 but not by FP receptors in the cat. These observations were further supported by the fact that fluprostenol, a more selective FP receptor agonist than PGF2α, did not lower IOP while contracting the sphincter muscle to induce miosis. If FP receptors were present in the ciliary body, fluprostenol would have reduced IOP as it contracted the sphincter muscles that are known to express FP receptors. Furthermore, the observation that the concurrent administration of PGF and 17-phenyl trinor PGE2 was not additive in lowering IOP indicated that these two agonists were acting primarily on the same EP1 receptors. If these two agonists were acting on separate receptor types, then the response to the combined treatment would have been greater than the response to either of the agonists alone. The order of potency of prostaglandins for EP1 receptors is PGE2 > PGF, prostacyclin > PGD2 and TXA2. 20 Therefore, in tissues in which FP receptors are lacking, PGF is most likely to activate EP1 receptors. Our pharmacological study in vivo only suggests that PGF is acting via EP1 receptors. To determine whether this is precisely the situation, additional in vitro studies on the contractile or relaxing response of the feline ciliary muscles to FP and EP1 receptor agonists are needed. 
Ligand binding assays and functional studies suggest that PGF has affinity for DP and EP3 receptors. 21 22 23 Also, stimulation of DP or EP3 receptors reduces IOP in rabbits, 22 23 and stimulation of TP receptors reduces IOP in beagle dogs. 24 Thus, to exclude the possibility that the IOP-lowering effect of PGF was due to the stimulation of either EP3 or DP receptors or both, we tested a potent and selective DP receptor antagonist, BWA868c. 25 At 25- to 100-fold greater concentration than its IC50, the DP receptor antagonist did not significantly modify PGF response, suggesting that DP receptors are not involved in the ocular hypotension induced by PGF. Although PGF has a poor affinity for TP receptors, to rule out the extreme possibility that PGF also stimulated these receptors, the effect of the TP receptor antagonist SQ29548 26 on the responses to PGF was examined. Even at high concentrations, this antagonist did not block PGF response. We could not test the effect of an EP3 receptor antagonist on PGF response because no such antagonists are available. Therefore, we suggest that PGF does not stimulate DP or TP receptors to lower IOP in cats. 
Previous studies have suggested that the reduction of IOP and relaxation of ciliary muscle of cats by PGF are not mediated by FP receptors. 11 12 13 Also, it has been reported that PGF does not increase inositol phosphate turnover in the feline ciliary muscles ex vivo. 14 All these studies suggest a lack of FP receptors in the feline ciliary body but do not describe prostaglandin receptors in cats that are activated by PGF to lower IOP. The data we obtained with fluprostenol, EP1 receptor antagonists, and concurrent administration of PGF and 17-phenyl trinor PGE2 suggest that FP receptors are not expressed in the feline ciliary muscles. However, studies on the expression of mRNA of FP receptors in the target tissues, such as the feline ciliary muscles, need to be performed to confirm our pharmacological observations. 
The concentrations of prostaglandins used in the present study appear to be high, and it could be argued that other prostaglandin receptors, particularly EP1 receptors, were stimulated by such high concentrations. In fact, the doses of prostaglandins used in the present study were smaller than those used in previous studies. 2 11 18 It should also be pointed out that a dose of a compound administered topically to the eye is diluted by tears and that only a fraction of the dilution permeates the cornea. Thus, the intraocular prostaglandin concentration will probably range only from 0.25% to 0.5% of the administered dose. 27 28 29 Therefore, the intraocular concentrations of the agonists at the doses used in the present study were probably in the range of 0.03 to 0.25μ g. Furthermore, the actual concentration of the agonist in the tissues of the uveoscleral pathway or the site of action of PGF or 17-phenyl trinor PGE2 is likely to be less than the total concentration in the intraocular tissues. Therefore, prostaglandin agonists, administered topically, most likely stimulated the receptors for which the agonist has primary affinity. This suggestion is supported by the fact that fluprostenol, at large doses of 25 to 50μ g, stimulated only FP receptors in the iris sphincter muscle, not EP1 or other prostaglandin receptors. 
At present, the mechanism of the ocular hypotensive action of the EP1 receptor agonist 17-phenyl trinor PGE2 on IOP is not known. In a recent study, Krauss et al. 30 observed that novel TP receptor agonists reduce IOP and increase aqueous humor outflow in dogs. TP receptor activation results in the increased turnover of inositol trisphosphates followed by mobilization of intracellular calcium, leading to the contraction of smooth muscle cells in the trabecular meshwork and ciliary muscles. These events may be the underlying mechanism of facility increase by TP receptor agonists. Stimulation of EP1 receptors also mobilizes intracellular calcium, thus it can be speculated that 17-phenyl trinor PGE2 has the same mechanism of action as TP receptor agonists in lowering IOP. However, such speculation needs to be explored in studies on aqueous humor dynamics. 
 
Figure 1.
 
The reduction of IOP in cats by a single dose of topically administered prostaglandin F, 17-phenyl trinor PGE2, and fluprostenol. The IOP values are expressed as the net of control minus treated. Each experiment at each concentration was done on three animals, and each experiment was done at least twice. Vertical bars are± SEM. *Significant difference between controls and treated at P < 0.05 level.
Figure 1.
 
The reduction of IOP in cats by a single dose of topically administered prostaglandin F, 17-phenyl trinor PGE2, and fluprostenol. The IOP values are expressed as the net of control minus treated. Each experiment at each concentration was done on three animals, and each experiment was done at least twice. Vertical bars are± SEM. *Significant difference between controls and treated at P < 0.05 level.
Figure 2.
 
Intraocular pressure of vehicle-treated eyes (A; n = 8) and contralateral eyes (B; ▪) of 50 μg PGF–treated groups (n = 8) and IOP of 100 μg SC19220–treated eyes (▾; n = 4). Vertical bars are ±SEM.
Figure 2.
 
Intraocular pressure of vehicle-treated eyes (A; n = 8) and contralateral eyes (B; ▪) of 50 μg PGF–treated groups (n = 8) and IOP of 100 μg SC19220–treated eyes (▾; n = 4). Vertical bars are ±SEM.
Figure 3.
 
The reduction of pupil diameter in cats by PGF (A), 17-phenyl trinor PGE2 (B), and fluprostenol (C) administered topically. The values are the net of those for control minus treated eyes. Each experiment at each concentration used three animals, and each experiment was done at least twice. Vertical bars are ±SEM. *Significant difference between controls and treated at P < 0.05 level.
Figure 3.
 
The reduction of pupil diameter in cats by PGF (A), 17-phenyl trinor PGE2 (B), and fluprostenol (C) administered topically. The values are the net of those for control minus treated eyes. Each experiment at each concentration used three animals, and each experiment was done at least twice. Vertical bars are ±SEM. *Significant difference between controls and treated at P < 0.05 level.
Table 1.
 
IC50 Values of Prostaglandin Receptor Antagonists, SC19220 (EP1), SC51089 (EP1), BWA868c (DP), and SQ29548 (TP), for the Inhibition of IOP and Pupil Response to PGF and 17-Phenyl Trinor PGE2 in Cats
Table 1.
 
IC50 Values of Prostaglandin Receptor Antagonists, SC19220 (EP1), SC51089 (EP1), BWA868c (DP), and SQ29548 (TP), for the Inhibition of IOP and Pupil Response to PGF and 17-Phenyl Trinor PGE2 in Cats
Agonist Antagonist IOP Decrease (mmHg)* Pupil Diameter Decrease (mm)*
50 μg PGF 0 5.0 ± 1.4 (4) 5.0 ± 1.5 (4)
SC19220 (μg)
25 4.2 ± 0.4 (8) 3.3 ± 1.0 (8)
50 3.5 ± 0.4 (8) 3.6 ± 0.7 (8)
100 3.1 ± 1.6 (8), † 4.0 ± 0.4 (8)
SC51089 (μg)
0 6.3 ± 0.3 (4) 5.75 ± 1.2 (4)
2.5 6.3 ± 0.4 (4) 4.8 ± 0.9 (4)
5 2.3 ± 0.4 (4), † 4.9 ± 0.6 (4)
10 1.3 ± 1.3 (4), † 4.8 ± 1.0 (4)
BWA868c (ng)
0 4.5 ± 1.0 (4) 4.2 ± 1.1 (4)
0.3 4.2 ± 0.5 (4) 2.7 ± 1.3 (4)
1.2 3.7 ± 0.2 (4) 2.7 ± 0.3 (4)
SQ29548 (ng)
0 4.3 ± 0.6 (4) 4.1 ± 0.7 (4)
0.48 3.7 ± 0.6 (4) 3.3 ± 1.1 (4)
0.96 3.3 ± 0.6 (4) 3.3 ± 1.4 (4)
SC19220 (μg)
1.25 μg PGF (isopropyl ester) 0 3.5 ± 0.1 (5) 5.2 ± 0.6 (5)
100 0.2 ± 0.1 (5), † 3.6 ± 0.7 (5)
50 μg 17-phenyl trinor PGE2 0 6.2 ± 1.5 (8) 3.5 ± 0.8 (8)
25 5.8 ± 0.9 (8) 3.3 ± 0.1 (8)
50 5.0 ± 1.2 (8) 2.0 ± 1.4 (8)
100 1.3 ± 1.1 (8), † 0.5 ± 0.4 (8), †
Figure 4.
 
The response of IOP to 12.5 μg of PGF and 17-phenyl trinor PGE2 administered alone or in combination. The IOP values are the net of those for control minus treated eyes. Each experiment consisted of six animals. Vertical bars are ±SEM.
Figure 4.
 
The response of IOP to 12.5 μg of PGF and 17-phenyl trinor PGE2 administered alone or in combination. The IOP values are the net of those for control minus treated eyes. Each experiment consisted of six animals. Vertical bars are ±SEM.
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Figure 1.
 
The reduction of IOP in cats by a single dose of topically administered prostaglandin F, 17-phenyl trinor PGE2, and fluprostenol. The IOP values are expressed as the net of control minus treated. Each experiment at each concentration was done on three animals, and each experiment was done at least twice. Vertical bars are± SEM. *Significant difference between controls and treated at P < 0.05 level.
Figure 1.
 
The reduction of IOP in cats by a single dose of topically administered prostaglandin F, 17-phenyl trinor PGE2, and fluprostenol. The IOP values are expressed as the net of control minus treated. Each experiment at each concentration was done on three animals, and each experiment was done at least twice. Vertical bars are± SEM. *Significant difference between controls and treated at P < 0.05 level.
Figure 2.
 
Intraocular pressure of vehicle-treated eyes (A; n = 8) and contralateral eyes (B; ▪) of 50 μg PGF–treated groups (n = 8) and IOP of 100 μg SC19220–treated eyes (▾; n = 4). Vertical bars are ±SEM.
Figure 2.
 
Intraocular pressure of vehicle-treated eyes (A; n = 8) and contralateral eyes (B; ▪) of 50 μg PGF–treated groups (n = 8) and IOP of 100 μg SC19220–treated eyes (▾; n = 4). Vertical bars are ±SEM.
Figure 3.
 
The reduction of pupil diameter in cats by PGF (A), 17-phenyl trinor PGE2 (B), and fluprostenol (C) administered topically. The values are the net of those for control minus treated eyes. Each experiment at each concentration used three animals, and each experiment was done at least twice. Vertical bars are ±SEM. *Significant difference between controls and treated at P < 0.05 level.
Figure 3.
 
The reduction of pupil diameter in cats by PGF (A), 17-phenyl trinor PGE2 (B), and fluprostenol (C) administered topically. The values are the net of those for control minus treated eyes. Each experiment at each concentration used three animals, and each experiment was done at least twice. Vertical bars are ±SEM. *Significant difference between controls and treated at P < 0.05 level.
Figure 4.
 
The response of IOP to 12.5 μg of PGF and 17-phenyl trinor PGE2 administered alone or in combination. The IOP values are the net of those for control minus treated eyes. Each experiment consisted of six animals. Vertical bars are ±SEM.
Figure 4.
 
The response of IOP to 12.5 μg of PGF and 17-phenyl trinor PGE2 administered alone or in combination. The IOP values are the net of those for control minus treated eyes. Each experiment consisted of six animals. Vertical bars are ±SEM.
Table 1.
 
IC50 Values of Prostaglandin Receptor Antagonists, SC19220 (EP1), SC51089 (EP1), BWA868c (DP), and SQ29548 (TP), for the Inhibition of IOP and Pupil Response to PGF and 17-Phenyl Trinor PGE2 in Cats
Table 1.
 
IC50 Values of Prostaglandin Receptor Antagonists, SC19220 (EP1), SC51089 (EP1), BWA868c (DP), and SQ29548 (TP), for the Inhibition of IOP and Pupil Response to PGF and 17-Phenyl Trinor PGE2 in Cats
Agonist Antagonist IOP Decrease (mmHg)* Pupil Diameter Decrease (mm)*
50 μg PGF 0 5.0 ± 1.4 (4) 5.0 ± 1.5 (4)
SC19220 (μg)
25 4.2 ± 0.4 (8) 3.3 ± 1.0 (8)
50 3.5 ± 0.4 (8) 3.6 ± 0.7 (8)
100 3.1 ± 1.6 (8), † 4.0 ± 0.4 (8)
SC51089 (μg)
0 6.3 ± 0.3 (4) 5.75 ± 1.2 (4)
2.5 6.3 ± 0.4 (4) 4.8 ± 0.9 (4)
5 2.3 ± 0.4 (4), † 4.9 ± 0.6 (4)
10 1.3 ± 1.3 (4), † 4.8 ± 1.0 (4)
BWA868c (ng)
0 4.5 ± 1.0 (4) 4.2 ± 1.1 (4)
0.3 4.2 ± 0.5 (4) 2.7 ± 1.3 (4)
1.2 3.7 ± 0.2 (4) 2.7 ± 0.3 (4)
SQ29548 (ng)
0 4.3 ± 0.6 (4) 4.1 ± 0.7 (4)
0.48 3.7 ± 0.6 (4) 3.3 ± 1.1 (4)
0.96 3.3 ± 0.6 (4) 3.3 ± 1.4 (4)
SC19220 (μg)
1.25 μg PGF (isopropyl ester) 0 3.5 ± 0.1 (5) 5.2 ± 0.6 (5)
100 0.2 ± 0.1 (5), † 3.6 ± 0.7 (5)
50 μg 17-phenyl trinor PGE2 0 6.2 ± 1.5 (8) 3.5 ± 0.8 (8)
25 5.8 ± 0.9 (8) 3.3 ± 0.1 (8)
50 5.0 ± 1.2 (8) 2.0 ± 1.4 (8)
100 1.3 ± 1.1 (8), † 0.5 ± 0.4 (8), †
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