|  Help  |  About  |  Contact Us

Publication : Evidence for a GPR18 Role in Diurnal Regulation of Intraocular Pressure.

First Author  Miller S Year  2016
Journal  Invest Ophthalmol Vis Sci Volume  57
Issue  14 Pages  6419-6426
PubMed ID  27893106 Mgi Jnum  J:254677
Mgi Id  MGI:6112572 Doi  10.1167/iovs.16-19437
Citation  Miller S, et al. (2016) Evidence for a GPR18 Role in Diurnal Regulation of Intraocular Pressure. Invest Ophthalmol Vis Sci 57(14):6419-6426
abstractText  Purpose: The diurnal cycling of intraocular pressure (IOP) was first described in humans more than a century ago. This cycling is preserved in other species. The physiologic underpinning of this diurnal variation in IOP remains a mystery, even though elevated pressure is indicated in most forms of glaucoma, a common cause of blindness. Once identified, the system that underlies diurnal variation would represent a natural target for therapeutic intervention. Methods: Using normotensive mice, we measured the regulation of ocular lipid species by the enzymes fatty acid amide hydrolase (FAAH) and N-arachidonoyl phosphatidylethanolamine phospholipase (NAPE-PLD), mRNA expression of these enzymes, and their functional role in diurnal regulation of IOP. Results: We now report that NAPE-PLD and FAAH mice do not exhibit a diurnal cycling of IOP. These enzymes produce and break down acylethanolamines, including the endogenous cannabinoid anandamide. The diurnal lipid profile in mice shows that levels of most N-acyl ethanolamines and, intriguingly, N-arachidonoyl glycine (NAGly), decline at night: NAGly is a metabolite of arachidonoyl ethanolamine and a potent agonist at GPR18 that lowers intraocular pressure. The GPR18 blocker O1918 raises IOP during the day when pressure is low, but not at night. Quantitative PCR analysis shows that FAAH mRNA levels rise with pressure, suggesting that FAAH mediates the changes in pressure. Conclusions: Our results support FAAH-dependent NAGly action at GPR18 as the physiologic basis of the diurnal variation of intraocular pressure in mice.
Quick Links:
 
Quick Links:
 

Expression

Publication --> Expression annotations

 

Other

11 Bio Entities

Trail: Publication

0 Expression