Bimatoprost and prostaglandin F2α selectively stimulate intracellular calcium signaling in different cat iris sphincter cells

Abstract Bimatoprost is a synthetic analog of prostaglandin F 2α ethanolamide (prostamide F 2α ), and shares a pharmacological profile consistent with that of the prostamides. Like prostaglandin F 2α carboxylic acid, bimatoprost potently lowers intraocular pressure in dogs, primates and humans. In order to distinguish its mechanism of action from prostaglandin F 2α , fluorescence confocal microscopy was used to examine the effects of bimatoprost, prostaglandin F 2α and 17-phenyl prostaglandin F 2α on calcium signaling in resident cells of digested cat iris sphincter, a tissue which exhibits contractile responses to both agonists. Constant superfusion conditions obviated effective conversion of bimatoprost. Serial challenge with 100 n m bimatoprost and prostaglandin F 2α consistently evoked responses in different cells within the same tissue preparation, whereas prostaglandin F 2α and 17-phenyl prostaglandin F 2α elicited signaling responses in the same cells. Bimatoprost-sensitive cells were consistently re-stimulated with bimatoprost only, and prostaglandin F 2α sensitive cells could only be re-stimulated with prostaglandin F 2α . The selective stimulation of different cells in the same cat iris sphincter preparation by bimatoprost and prostaglandin F 2α , along with the complete absence of observed instances in which the same cells respond to both agonists, strongly suggests the involvement of distinct receptors for prostaglandin F 2α and bimatoprost. Further, prostaglandin F 2α but not bimatoprost potently stimulated calcium signaling in isolated human embryonic kidney cells stably transfected with the feline- and human-prostaglandin F 2α FP-receptor and in human dermal fibroblast cells, and only prostaglandin F 2α competed with radioligand binding in HEK-feFP cells. These studies provide further evidence for the existence of a bimatoprost-sensitive receptor that is distinct from any of the known prostaglandin receptor types.