May 2008
Volume 49, Issue 13
ARVO Annual Meeting Abstract  |   May 2008
Pharmacological Characterization of Prostaglandin-Induced Contraction of Feline Iris Sphincter Smooth Muscle Strips in vitro
Author Affiliations & Notes
  • N. A. Sharif
    Pharmacology, Alcon Research Ltd, Fort Worth, Texas
  • I. Kaddour-Djebbar
    Biochemistry & Mol. Biology, Medical College of Georgia, Augusta, Georgia
  • A. Abdel-Latif
    Biochemistry & Mol. Biology, Medical College of Georgia, Augusta, Georgia
  • Footnotes
    Commercial Relationships  N.A. Sharif, Alcon Research, Ltd., E; I. Kaddour-Djebbar, None; A. Abdel-Latif, None.
  • Footnotes
    Support  None.
Investigative Ophthalmology & Visual Science May 2008, Vol.49, 2617. doi:
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      N. A. Sharif, I. Kaddour-Djebbar, A. Abdel-Latif; Pharmacological Characterization of Prostaglandin-Induced Contraction of Feline Iris Sphincter Smooth Muscle Strips in vitro. Invest. Ophthalmol. Vis. Sci. 2008;49(13):2617.

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      © ARVO (1962-2015); The Authors (2016-present)

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Purpose: : To determine the potency and intrinsic activities of FP-class prostaglandins (PGs) in their ability to cause the contraction of feline iris sphincter muscle in vitro.

Methods: : Standard organ-bath-based experiments were conducted on freshly obtained cat iris sphincter muscle strips maintained in oxygenated Krebs-Ringer bicarbonate buffer. The ability of cumulatively-added increasing concentrations of various free acids, ester and amide forms of some synthetic and natural PGs to elicit tissue contractions were monitored using force-transducers hooked up to the sphincter muscle strips.

Results: : The relative agonist potencies (EC50) of the compounds were: cloprostenol (0.0012 ± 0.0004 nM) >> travoprost acid (0.46 ± 0.13 nM) = bimatoprost acid (0.99 ± 0.19 nM) > (±)-fluprostenol (15.8 ± 2.6 nM) = PGF2α (18.6 ± 1.8 nM) > latanoprost acid (29.9 ± 1.6 nM) > bimatoprost (140 ± 45 nM) > S-1033 (588 ± 39 nM) > unoprostone (UF-021; 1280 ± 50 nM) (n = 4-14). The maximum response induced by travoprost acid (122 ± 2.3% max. response relative to PGF2α) was significantly greater than that induced by all the other PG compounds (p < 0.001 - p < 0.02). Interestingly, the FP-receptor antagonist, AL-8810, behaved as a moderate efficacy partial agonist (EC50 = 2140 ± 190 nM; 63 ± 4.3% max. response relative to PGF2α), indicating that the cat iris contains an extremely well coupled FP receptor population and/or the tissue contains an extremely high density of the FP receptors and/or spare FP receptors. The cat iris contraction data were well correlated with other FP receptor-mediated signal transduction processes including FP-receptor binding in bovine corpus luteum (r = 0.86), FP-receptor binding in human iris (r = 0.61), phosphoinositide (PI) hydrolysis in human ciliary muscle and trabecular meshwork cells (r = 0.77 - 0.86), PI turnover in rat and mouse cells (r = 0.73 - 0.76) and via cloned human FP receptor (r = 0.9), and rat uterus contraction (r = 0.84).

Conclusions: : The present studies have demonstrated the presence of extremely well coupled FP-receptors in cat iris sphincter smooth muscle that mediate contractions induced by free acid, ester and amide forms of the FP-class PGs. The high sensitivity of these FP receptors appears to be one explanation for the picomolar potency of cloprostenol and the relatively high potency of bimatoprost, and the high intrinsic activity (Emax) of travoprost acid and AL-8810.

Keywords: receptors: pharmacology/physiology • signal transduction: pharmacology/physiology • anterior chamber 

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