Prostanoid EP4 receptor stimulation produces ocular hypotension by a mechanism that does not appear to involve uveoscleral outflow.

Purpose: As part of a systematic elucidation of the pharmacology of prostaglandin's (PG) effects on intraocular pressure in the monkey, the prototypical selective prostanoid EP(4) receptor agonist (3,7-dithia PGE(1)) was examined. It was found to be highly efficacious in nonhuman primates, and its mechanism of ocular hypotensive activity was investigated.

Methods: Intraocular pressure (IOP) was measured by pneumatonometry in conscious monkeys restrained in custom-designed chairs.

Bimatoprost and prostaglandin F(2 alpha) selectively stimulate intracellular calcium signaling in different cat iris sphincter cells.

Bimatoprost is a synthetic analog of prostaglandin F(2 alpha) ethanolamide (prostamide F(2 alpha)), and shares a pharmacological profile consistent with that of the prostamides. Like prostaglandin F(2 alpha) carboxylic acid, bimatoprost potently lowers intraocular pressure in dogs, primates and humans. In order to distinguish its mechanism of action from prostaglandin F(2 alpha), fluorescence confocal microscopy was used to examine the effects of bimatoprost, prostaglandin F(2 alpha) and 17-phenyl prostaglandin F(2 alpha) on calcium signaling in resident cells of digested cat iris sphincter, a tissue which exhibits contractile responses to both agonists.

Vascular activities of prostaglandins and selective prostanoid receptor agonists in human retinal microvessels.

Prostanoid analogs have recently been introduced into clinical use for the management of increased intraocular pressure (IOP). This class of compounds is known to exert effects on vascular components and some endogenous parent prostaglandins have been shown to alter regional ocular blood flow and exhibit significant vasoactive properties in isolated ocular blood vessels, so the possibility exists that prostanoids could affect the ocular microcirculation either by absorption into the systemic circulation or by direct localized activity on the retinal microvasculature. Thus, the aim of this study was to examine systematically the effects of a broad variety of agonists that exhibit preferential activity at EP(1)-, EP(2)-, EP(3)-, FP-, DP-, IP-, and TP-prostanoid receptor sites on microvessel caliber in the microvasculature associated with human retinal tissues grafted into the hamster cheek pouch membrane.