Effects of latanoprost and GLC756, a novel dopamine D2 agonist and D1 antagonist, on cultured normal human dermal fibroblasts.
OBJECTIVE
Proliferation of subconjunctival fibroblasts plays a critical role in scarring and failure of glaucoma filtering surgery. Long-term topical glaucoma medications appear to increase fibroblast proliferation. In this study, the effects of topical antiglaucoma drugs latanoprost and GLC756, a novel dopamine D2 agonist and D1 antagonist, on cultured normal human dermal fibroblasts (NHDF) were examined.


METHODS
The NHDF cell line was incubated with latanoprost, prostaglandin F2alpha (PGF2alpha), GLC756, or 5-fluorouracil as a positive control at concentrations of 3 and 30 microM for 6, 18, and 24 hours. Fibroblast growth was measured by 5-bromodeoxyuridine (BrdU) uptake using laser scanning cytometry.


RESULTS
Latanoprost and PGF2alpha had a biphasic response on the number of cultured NHDF positively stained with BrdU. A stimulating effect on proliferation occurred early, 6 hours after incubation, and an inhibitory effect 18 to 24 hours after incubation. GLC756, in contrast, revealed only inhibitory effects on BrdU uptake 18 to 24 hours after incubation. The pattern of GLC756 was similar to that of the positive control 5-fluorouracil.


CONCLUSIONS
Latanoprost seemed to have a biphasic response on the proliferation of cultured NHDF. First there was a stimulating thereafter a secondary negative modulating effect. GLC756 had a fully antiproliferative effect on the NHDF, indicating an additional potential of novel dopamine compounds for topical glaucoma medication.
Department of Toxicology/Pathology, Novartis Pharma AG, Basel, Switzerland.
U W
UW
Laengle
R
R
Markstein
D
D
Pralet
B
B
Greiner
D
D
Roman
D000959:Antihypertensive Agents / Q000494:pharmacology*; D001973:Bromodeoxyuridine / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004261:DNA Replication; D020405:Dermis / Q000166:cytology / Q000187:drug effects*; D015237:Dinoprost / Q000494:pharmacology; D005347:Fibroblasts / Q000187:drug effects; D005434:Flow Cytometry; D019084:Fluorescent Antibody Technique, Indirect; D005472:Fluorouracil / Q000494:pharmacology; D006801:Humans; D000077338:Latanoprost; D011461:Prostaglandins F, Synthetic / Q000494:pharmacology*; D011804:Quinolines / Q000494:pharmacology*; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors*; D017448:Receptors, Dopamine D2 / Q000819:agonists*
D000959:Antihypertensive Agents; D011461:Prostaglandins F, Synthetic; D011804:Quinolines; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; C102871:SDZ GLC 756; D000077338:Latanoprost; D015237:Dinoprost; D001973:Bromodeoxyuridine; D005472:Fluorouracil