Bimatoprost-induced calcium signaling in human T-cells does not involve prostanoid FP or TP receptors.
OBJECTIVE
The prostamide bimatoprost and prostanoid FP receptor agonists are highly efficacious drugs for glaucoma treatment. The presence of both prostamide and prostanoid FP receptors in bimatoprost-sensitive preparations has made prostamide receptor classification difficult. This study investigated a novel bimatoprost-sensitive preparation.


METHODS
Human peripheral blood T lymphoblasts (Molt-3) and human osteoblasts (hFOB) were cultured for intracellular calcium signaling studies and quantitative real-time PCR analysis of RNA.


RESULTS
Bimatoprost stimulated concentration-related increases in [Ca(2 +)](i) in a human T-cell line that does not express human FP receptor/variants, according to PCR analysis. The calcium signal induced by bimatoprost was not antagonized by prostanoid FP receptor antagonist/partial agonist AL-8810 or selective TP receptor antagonist SQ 29548. Conversely, bimatoprost did not elevate [Ca(2 +)](i) in human osteoblasts, which were confirmed to contain RNA of human FP receptor/variants.


CONCLUSIONS
Molt-3 cells have been identified as a bimatoprost-sensitive preparation in which the activity of bimatoprost is independent of prostanoid FP receptors.
Chen
June
J
Department of Biological Sciences, Allergan, Inc., Irvine, California 92612, USA. chen_june@allergan.com
Lu
Ryan Ta
RT
Lai
Ronald
R
Dinh
Tim
T
Paul
David
D
Venadas
Steven
S
Wheeler
Larry A
LA
D000577:Amides / Q000494:pharmacology*; D000959:Antihypertensive Agents / Q000494:pharmacology*; D000069580:Bimatoprost; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival; D002478:Cells, Cultured; D003008:Cloprostenol / Q000031:analogs & derivatives* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D010006:Osteoblasts / Q000378:metabolism; D011982:Receptors, Prostaglandin / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D017482:Receptors, Thromboxane / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000378:metabolism*
D000577:Amides; D000959:Antihypertensive Agents; D011982:Receptors, Prostaglandin; D017482:Receptors, Thromboxane; C034671:prostaglandin F2alpha receptor; D003008:Cloprostenol; D000069580:Bimatoprost; D002118:Calcium