Effects of latanoprost, timolol and GLC756, a novel dopamine D(2) agonist and D(1) antagonist on LTC(4) release after rat mast cell activation.
OBJECTIVE
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 D(2) agonist and D(1) antagonist, on leukotriene C(4) (LTC(4)) 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 microM. LTC(4) concentration in supernatant was assessed 5 h post activation by EIA.


RESULTS
Compared with controls, timolol showed no relevant effect on LTC(4) release, 5 h after mast cell activation. Latanoprost and GLC756, in contrast, revealed an inhibitory effect on LTC(4) release, which was dose-related and statistically significant at the concentrations of 10 and 30 microM.


CONCLUSIONS
The results of this study suggest that timolol has no significant influence on LTC(4) release from activated mast cells. By contrast, latanoprost and GLC756 inhibited LTC(4) release, suggesting a possible anti-inflammatory effect on ocular allergic inflammatory processes in topical glaucoma medication.
Laengle
Ulrich W
UW
Department of Toxicology/Pathology, Novartis Pharma AG, Basel, Switzerland.
Markstein
Rudolf
R
Pralet
Dominique
D
Seewald
Wolfgang
W
Roman
Danielle
D
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000494:pharmacology; D045744:Cell Line, Tumor; D015259:Dopamine Agents / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D007073:Immunoglobulin E / Q000276:immunology; D000077338:Latanoprost; D017997:Leukotriene C4 / Q000378:metabolism*; D008407:Mast Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D009994:Osmolar Concentration; D011461:Prostaglandins F, Synthetic / Q000008:administration & dosage / Q000494:pharmacology*; D011804:Quinolines / Q000494:pharmacology*; D051381:Rats; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors; D017448:Receptors, Dopamine D2 / Q000819:agonists; D013999:Timolol / Q000008:administration & dosage / Q000494:pharmacology*
D000888:Antibodies, Anti-Idiotypic; D015259:Dopamine Agents; D011461:Prostaglandins F, Synthetic; D011804:Quinolines; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; C102871:SDZ GLC 756; D017997:Leukotriene C4; D007073:Immunoglobulin E; D000077338:Latanoprost; D013999:Timolol