Human ciliary muscle cell responses to FP-class prostaglandin analogs: Phosphoinositide hydrolysis, intracellular Ca2+ mobilization and MAP kinase activation

Phospholipase C induced phosphoinositide (PI) turnover, intracellular Ca2+ ([Ca2+]i) mobilization and mitogen-activated protein (MAP) kinase activation by FP-class prostaglandin analogs was studied in normal human ciliary muscle (h-CM) cells. Agonist potencies obtained in the PI turnover assays were: travoprost acid ((+)-fluprostenol; EC50 = 2.6 ± 0.8 nM) > bimatoprost acid (EC50 = 3.6 ± 1.2 nM) > (±)-fluprostenol (EC50 = 4.3 ± 1.3 nM) >> prostaglandin F2α (PGF2α) (EC50 = 134 ± 17 nM) > latanoprost acid (EC50 = 198 ± 83 nM) > S-1033 (EC50 = 2930 ± 1420 nM) > unoprostone (EC50 = 5590 ± 1490 nM) > bimatoprost (EC50 = 9600 ± 1100 nM). Agonist potencies in h-CM cells correlated well with those previously obtained for the cloned human ciliary body-derived FP receptor (r = 0.96, p< 0.001) and that present on h-TM cells (r = 0.94, p< 0.0001). Travoprost acid, PGF2α and unoprostone also stimulated [Ca2+]i mobilization in h-CM cells with travoprost acid being the most potent agonist. MAP kinase activity was stimul...