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Abstract #15265 Published in IGR 8-4
Effect of GLC756, a novel mixed dopamine D1 receptor antagonist and dopamine D2 receptor agonist, on TNF-α release in vitro from activated rat mast cells
Laengle UW; Markstein R; Pralet D; Seewald W; Roman DExperimental Eye Research 2006; 83: 1335-1339
Tumor necrosis factor-α (TNF-α) is released from activated mast cells via an IgE-dependent mechanisms, and plays a crucial role in ocular allergic inflammation. This study examined the influence of three antiglaucoma drugs differing in their chemical structure and pharmacological profile (i.e., latanoprost, timolol, GLC756) on TNF-α release from activated rat mast cells. A rat basophilic leukemia mast cell line (RBL-2H3) was activated via IgE/anti-IgE. Rat mast cells were incubated with latanoprost, timolol, GLC756 or betamethasone (positive control) at concentrations of 0.1, 1, 10 and 30 μM. TNF-α concentration in supernatant was measured by ELISA 5 h post-activation. Compared to controls, the prostaglandin derivative latanoprost and the beta-blocker timolol in the concentration range 0.1-30 μM, had no significant effect on TNF-α release from rat mast cells measured 5h after activation. By contrast, the dopaminergic drug GLC756 compared to controls in the concentration range 1-30 μM significantly inhibited TNF-α release from activated rat mast cells in a concentration-dependent manner. The positive control betamethasone inhibited TNF-α release almost completely at all concentrations tested. In conclusion, the results of this study suggest that latanoprost and timolol do not reduce inflammation triggered by activated mast cells. By contrast, the dopaminergic drug GLC756 inhibited TNF-α release from activated mast cells, suggesting an palliative potential of dopaminergic compounds on allergic conjunctivitis in topical glaucoma medication.
Dr. U.W. Laengle, Department of Toxicology/Pathology, Novartis Pharma AG, Basel, Switzerland
Classification:
11.14 Investigational drugs; pharmacological experiments (Part of: 11 Medical treatment)
2.1 Conjunctiva (Part of: 2 Anatomical structures in glaucoma)
3.10 Immunobiology (Part of: 3 Laboratory methods)
