Bimatoprost and its free acid are prostaglandin FP receptor agonists.
Bimatoprost (17-phenyl-prostaglandin F(2alpha) ethyl amide) has been reported not to exert its actions via prostaglandin receptors. Here, bimatoprost displaced [3H]prostaglandin F(2alpha) from FP receptors (K(i)=6310+/-1650 nM). Bimatoprost rapidly mobilized intracellular Ca(2+) ([Ca(2+)](i)) via cloned human FP receptors expressed in human embryonic kidney cells (EC(50)=2940+/-1663 nM) and via native FP receptors in 3T3 mouse fibroblasts (EC(50)=2200+/-670 nM). Furthermore, AL-8810 ((5Z, 13E)-(9S,11S,15R)-9,15-dihydroxy-11-fluoro-15-(2-indanyl)-16,17,18,19,20-pentanor-5,13-prostadienoic acid), an FP receptor antagonist, blocked the bimatoprost-induced [Ca(2+)](i) mobilization.
Sharif
N A
NA
Molecular Pharmacology Unit, Alcon Research, Ltd., 6201 South Freeway, Fort Worth, TX 76134, USA. naj.sharif@alconlabs.com
Williams
G W
GW
Kelly
C R
CR
D016475:3T3 Cells; D000577:Amides; D000818:Animals; D000069580:Bimatoprost; D001667:Binding, Competitive / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D003008:Cloprostenol / Q000031:analogs & derivatives; D015237:Dinoprost / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D050356:Lipid Metabolism; D008055:Lipids / Q000494:pharmacology; D051379:Mice; D011982:Receptors, Prostaglandin / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014316:Tritium
D000577:Amides; D008055:Lipids; D011982:Receptors, Prostaglandin; C034671:prostaglandin F2alpha receptor; D014316:Tritium; C121227:AL 8810; D003008:Cloprostenol; D015237:Dinoprost; D000069580:Bimatoprost; D002118:Calcium