{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T16:39:39Z","timestamp":1781800779456,"version":"3.54.5"},"reference-count":40,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2013,5,27]],"date-time":"2013-05-27T00:00:00Z","timestamp":1369612800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2013,6]]},"abstract":"Background and Purpose<\/jats:title>GPR<\/jats:styled-content>18 is a recently deorphaned lipid receptor that is activated by the endogenous lipid N<\/jats:styled-content><\/jats:italic>\u2010arachidonoyl glycine (NAG<\/jats:styled-content>ly) as well the behaviourally inactive atypical cannabinoid, abnormal cannabidiol (A<\/jats:styled-content>bn\u2010CBD<\/jats:styled-content>). The presence and\/or function of any GPR<\/jats:styled-content>18\u2010based ocular signalling system remain essentially unstudied. The objectives of this research are: (i) to determine the disposition of GPR<\/jats:styled-content>18 receptors and ligands in anterior murine eye, (ii) examine the effect of GPR<\/jats:styled-content>18 activation on intraocular pressure (IOP<\/jats:styled-content>) in a murine model, including knockout mice for CB1<\/jats:sub><\/jats:styled-content>, CB2<\/jats:sub><\/jats:styled-content> and GPR<\/jats:styled-content>55.<\/jats:p><\/jats:sec>Experimental Approach<\/jats:title>IOP<\/jats:styled-content> was measured in mice following topical application of A<\/jats:styled-content>bn\u2010CBD<\/jats:styled-content>, NAG<\/jats:styled-content>ly or the GPR<\/jats:styled-content>55\/GPR<\/jats:styled-content>18 agonist O<\/jats:styled-content>\u20101602, alone or with injection of the GPR<\/jats:styled-content>18 antagonist, O<\/jats:styled-content>\u20101918. GPR<\/jats:styled-content>18 protein localization was assessed with immunohistochemistry. Endocannabinoids were measured using LC<\/jats:styled-content>\/MS\u2010MS<\/jats:styled-content>.<\/jats:p><\/jats:sec>Key Results<\/jats:title>GPR<\/jats:styled-content>18 protein was expressed most prominently in the ciliary epithelium and the corneal epithelium and, interestingly, in the trabecular meshwork. The GPR<\/jats:styled-content>18 ligand, NAG<\/jats:styled-content>ly, was also detected in mouse eye at a level comparable to that seen in the brain. Abn\u2010CBD<\/jats:styled-content> and NAG<\/jats:styled-content>ly, but not O<\/jats:styled-content>\u20101602, significantly reduced IOP<\/jats:styled-content> in all mice tested. The antagonist, O<\/jats:styled-content>\u20101918, blocked the effects of Abn\u2010CBD<\/jats:styled-content> and NAG<\/jats:styled-content>ly.<\/jats:p><\/jats:sec>Conclusions and Implications<\/jats:title>We present evidence for a functional GPR<\/jats:styled-content>18\u2010based signalling system in the murine anterior eye, including receptors and ligands. GPR<\/jats:styled-content>18 agonists, Abn\u2010CBD<\/jats:styled-content> and NAG<\/jats:styled-content>ly, reduce IOP<\/jats:styled-content> independently of CB1<\/jats:sub><\/jats:styled-content>, CB2<\/jats:sub><\/jats:styled-content> or GPR<\/jats:styled-content>55. These findings suggest that GPR<\/jats:styled-content>18 may serve as a desirable target for the development of novel ocular hypotensive medications.<\/jats:p><\/jats:sec>Linked Articles<\/jats:title>This article is part of a themed section on Cannabinoids. To view the other articles in this section visit http:\/\/dx.doi.org\/10.1111\/bph.2013.169.issue\u20104<\/jats:ext-link> & http:\/\/dx.doi.org\/10.1111\/bph.2012.167.issue\u20108<\/jats:ext-link><\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.12136","type":"journal-article","created":{"date-parts":[[2013,3,6]],"date-time":"2013-03-06T03:55:14Z","timestamp":1362542114000},"page":"834-843","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":59,"title":["A GPR<\/scp>18\u2010based signalling system regulates IOP<\/scp> in murine eye"],"prefix":"10.1111","volume":"169","author":[{"given":"Meggie D.","family":"Caldwell","sequence":"first","affiliation":[{"name":"Department of Clinical Vision Science Dalhousie University Halifax NS Canada"},{"name":"Department of Ophthalmology Dalhousie University Halifax NS Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sherry 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