PMID- 16965772
OWN - NLM
STAT- MEDLINE
DCOM- 20070220
LR  - 20181201
IS  - 0014-4835 (Print)
IS  - 0014-4835 (Linking)
VI  - 83
IP  - 6
DP  - 2006 Dec
TI  - Effect of GLC756, a novel mixed dopamine D1 receptor antagonist and dopamine D2 
      receptor agonist, on TNF-alpha release in vitro from activated rat mast cells.
PG  - 1335-9
AB  - Tumor necrosis factor-alpha (TNF-alpha) 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-alpha 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 microM. 
      TNF-alpha 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 microM, had no significant 
      effect on TNF-alpha release from rat mast cells measured 5h after activation. By 
      contrast, the dopaminergic drug GLC756 compared to controls in the concentration 
      range 1-30 microM significantly inhibited TNF-alpha release from activated rat 
      mast cells in a concentration-dependent manner. The positive control 
      betamethasone inhibited TNF-alpha 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-alpha release from activated 
      mast cells, suggesting an palliative potential of dopaminergic compounds on 
      allergic conjunctivitis in topical glaucoma medication.
FAU - Laengle, Ulrich Wilhelm
AU  - Laengle UW
AD  - Department of Toxicology/Pathology, Novartis Pharma AG, Basel, Switzerland.
FAU - Markstein, Rudolf
AU  - Markstein R
FAU - Pralet, Dominique
AU  - Pralet D
FAU - Seewald, Wolfgang
AU  - Seewald W
FAU - Roman, Danielle
AU  - Roman D
LA  - eng
PT  - Journal Article
DEP - 20060911
PL  - England
TA  - Exp Eye Res
JT  - Experimental eye research
JID - 0370707
RN  - 0 (Antihypertensive Agents)
RN  - 0 (Prostaglandins F, Synthetic)
RN  - 0 (Quinolines)
RN  - 0 (Receptors, Dopamine D1)
RN  - 0 (Receptors, Dopamine D2)
RN  - 0 (SDZ GLC 756)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 6Z5B6HVF6O (Latanoprost)
RN  - 817W3C6175 (Timolol)
SB  - IM
MH  - Animals
MH  - Antihypertensive Agents/pharmacology
MH  - Cell Death/drug effects
MH  - Dose-Response Relationship, Drug
MH  - Latanoprost
MH  - Mast Cells/*drug effects/metabolism
MH  - Prostaglandins F, Synthetic/pharmacology
MH  - Quinolines/*pharmacology
MH  - Rats
MH  - Receptors, Dopamine D1/*antagonists & inhibitors
MH  - Receptors, Dopamine D2/*agonists
MH  - Timolol/pharmacology
MH  - Tumor Cells, Cultured
MH  - Tumor Necrosis Factor-alpha/*metabolism
EDAT- 2006/09/13 09:00
MHDA- 2007/02/21 09:00
CRDT- 2006/09/13 09:00
PHST- 2006/04/26 00:00 [received]
PHST- 2006/07/12 00:00 [revised]
PHST- 2006/07/17 00:00 [accepted]
PHST- 2006/09/13 09:00 [pubmed]
PHST- 2007/02/21 09:00 [medline]
PHST- 2006/09/13 09:00 [entrez]
AID - S0014-4835(06)00309-5 [pii]
AID - 10.1016/j.exer.2006.07.008 [doi]
PST - ppublish
SO  - Exp Eye Res. 2006 Dec;83(6):1335-9. doi: 10.1016/j.exer.2006.07.008. Epub 2006 
      Sep 11.