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Effects of latanoprost, timolol and GLC756, a novel dopamine D2 agonist and D1 antagonist on LTC4 release after rat mast cell activation

Authors


Dr Danielle Roman, Novartis Pharma AG, Department of Toxicology/Pathology, MUT-2881.233, CH-4002 Basel, Switzerland. Email: danielle.roman@novartis.com

Abstract

Purpose:  Mast cells participate in ocular allergic inflammation by releasing biologically active mediators. Leukotrienes are released from activated mast cells via an IgE-dependent mechanism, and play a crucial role in ocular allergic inflammation. In this study, the effect of three topical antiglaucoma drugs, that is, latanoprost, timolol and GLC756, a novel dopamine D2 agonist and D1 antagonist, on leukotriene C4 (LTC4) release after rat mast cell activation was examined.

Methods:  A rat basophilic leukaemia RBL-2H3 mast cell line was activated via IgE/anti-IgE. Rat mast cells were incubated with latanoprost, timolol, or GLC756 at concentrations of 0.1, 1, 10 and 30 μM. LTC4 concentration in supernatant was assessed 5 h post activation by EIA.

Results:  Compared with controls, timolol showed no relevant effect on LTC4 release, 5 h after mast cell activation. Latanoprost and GLC756, in contrast, revealed an inhibitory effect on LTC4 release, which was dose-related and statistically significant at the concentrations of 10 and 30 μM.

Conclusion:  The results of this study suggest that timolol has no significant influence on LTC4 release from activated mast cells. By contrast, latanoprost and GLC756 inhibited LTC4 release, suggesting a possible anti-inflammatory effect on ocular allergic inflammatory processes in topical glaucoma medication.

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