Identification of an antagonist that selectively blocks the activity of prostamides (prostaglandin‐ethanolamides) in the feline iris

Abstract

Background and Purpose: The prostamides (prostaglandin-ethanolamides) and prostaglandin (PG) glyceryl esters are biosynthesized by COX-2 from the respective endocannabinoids anandamide and 2-arachidonyl glycerol. Agonist studies suggest that their pharmacologies are unique and unrelated to prostanoid receptors. This concept was further investigated using antagonists. Experimental Approach: The isolated feline iris was used as a key preparation, where prostanoid FP receptors and prostamide activity co-exist. Activity at human recombinant FP and other prostanoid receptors was determined using stable transfectants.

Identification of prostamides, fatty acyl ethanolamines, and their biosynthetic precursors in rabbit cornea

“…PGF 2 ␣ -EA is involved in infl ammatory pain and dorsal horn nociceptive neuron excitability, while PGE 2 -EA increases blood fl ow and reduces mean arterial pressure in the renal medulla, exhibits strong neuroprotective properties in cerebellar neurons, and along with PGD 2 -EA, induces apoptosis in an in vitro model of colorectal carcinoma (18)(19)(20)(21). Prostamides do not show potent interaction with prostanoid receptors, and studies using isolated feline iris cells have suggested the presence of prostamide-sensitive receptors different from the ones responding to PGs (22)(23)(24). The prostamide precursor A-EA has also been shown to exhibit neuroprotective and analgesic roles in infl ammation and pain models ( 25,26 ), Instrument control and data acquisition were performed using the MassLynx™ V4.0 software.…”

Endogenous bioactive lipids and the regulation of conventional outflow facility

“…The recent availability of prostamide-specific antagonists has enabled further characterization of prostamide pharmacology and functional activity [34,96,97]. AGN 211334, a second generation prostamide antagonist, specifically blocks the effects of prostamide F 2α and bimatoprost but not PGF 2α and FP receptor agonists in the feline iris [34,96].…”

The Endocannabinoid System: Current Pharmacological Research and Therapeutic Possibilities

“…A final note concerns the recent report that the analgesic and antiand since an antagonist of the actions of prostamide F 2a upon the pyretic agent acetaminophen is transformed via deacylation folcat iris sphincter has been discovered (Woodward et al 2005). A lowed by fatty acid amide hydrolase-dependent arachidonic acid cyclooxygenase product of anandamide also inhibits secretion of inconjugation to give the anandamide transport inhibitor/TRPV1 terleukin-2 from primary splenocytes (Rockwell & Kaminski 2004) agonist AM404 (N-(4-hydroxyphenyl)arachidonoylamide) (Höge-and produces pulmonary hypertension in isolated rabbit lungs stätt et al 2005).…”

“…Cyclooxygenase-2 and lipoxygenase derived metabolites of anandamide and 2-arachidonoylglycerol Whilst the main route of metabolism of anandamide and 2-arachition of the cat iris sphincter (in a manner not blocked by the prostadonoylglycerol is by hydrolysis to arachidonic acid, there is increasmide antagonist described above) in vitro (Woodward et al 2005). ing evidence that cyclooxygenase-2 and lipoxygenase pathways Given that the endocannabinoids can interact with cyclooxygenmay be important, not so much as for the removal of these endoase-2, it is perhaps not surprising that compounds that inhibit cyclocannabinoids (although there is evidence in the hippocampus that oxygenase enzymes also have effects upon the endocannabinoid sys-COX-2 inhibition potentiates endocannabinoid retrograde signaltem.…”